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    Sulfonamide and Trimethoprim Antibiotic Combinations

    DEA CLASS

    Rx

    DESCRIPTION

    Combination product of trimethoprim and sulfamethoxazole in a fixed 1:5 ratio; both are synthetic folate antagonists.

    COMMON BRAND NAMES

    Bacter-Aid DS, Bactrim, Bactrim DS, Septra, Septra DS, Sulfatrim, Sulfatrim Pediatric, Sultrex Pediatric

    HOW SUPPLIED

    Bacter-Aid DS/Bactrim/Bactrim DS/Septra/Septra DS/Sulfamethoxazole, Trimethoprim Oral Tab: 400-80mg, 800-160mg
    Septra/Sulfamethoxazole, Trimethoprim/Sulfatrim/Sulfatrim Pediatric/Sultrex Pediatric Oral Susp: 5mL, 200-40mg
    Sulfamethoxazole, Trimethoprim Intravenous Inj Sol: 1mL, 80-16mg

    DOSAGE & INDICATIONS

    For the treatment of urinary tract infection (UTI), including pyelonephritis and cystitis.
    Oral dosage
    Adults

    160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours. The Infectious Diseases Society of America (IDSA) recommends a 3 day treatment course for acute, uncomplicated cystitis and a 14 day treatment course for pyelonephritis in female patients. For catheter-associated UTIs, the IDSA suggests that 7 days is appropriate for patients who have prompt resolution of symptoms and 10 to 14 days is recommended for those with a delayed response. The FDA-labeled duration for UTIs in general is 10 to 14 days.

    Children and Adolescents 3 to 17 years

    8 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 160 mg trimethoprim/800 mg sulfamethoxazole per dose) for 10 days.

    Infants and Children 2 months to 2 years

    6 to 12 mg/kg/day (trimethoprim component) PO divided every 12 hours for 7 to 14 days is recommended by the American Academy of Pediatrics (AAP) for the treatment of initial febrile UTI in infants and young children. The FDA-approved dosing is 8 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 160 mg trimethoprim/800 mg sulfamethoxazole per dose) for 10 days.

    Intravenous dosage
    Adults

    For severe infections, the manufacturer recommends 8 to 10 mg/kg/day (trimethoprim component) IV in 2 to 4 equally divided doses for up to 14 days. The Infectious Diseases Society of America (IDSA) recommends a 14 day treatment course for pyelonephritis in female patients. For catheter-associated UTIs, the IDSA suggests that 7 days is appropriate for patients who have prompt resolution of symptoms and 10 to 14 days is recommended for those with a delayed response.

    Infants, Children, and Adolescents 2 months to 17 years

    8 to 10 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for up to 14 days (Max: 960 mg trimethoprim/4,800 mg sulfamethoxazole per day) is recommended in FDA-approved labeling for severe infections.

    For the treatment of Pneumocystis pneumonia (PCP).
    Intravenous or Oral dosage
    Adults, Adolescents, Children, and Infants > 2 months

    15—20 mg/kg/day (trimethoprim component) IV or PO administered in divided doses every 6—8 hours. For HIV-infected patients, the HIV guidelines recommend a treatment duration of 21 days then chronic suppressive therapy. The FDA-labeled duration is 14—21 days for oral therapy and up to 14 days for IV therapy.

    For Pneumocystis pneumonia (PCP) prophylaxis in individuals who are immunosuppressed and considered to be at an increased risk.
    For primary PCP prophylaxis in HIV-infected patients.
    Oral dosage
    Adults and Adolescents

    160 mg trimethoprim; 800 mg sulfamethoxazole PO once daily or 80 mg trimethoprim; 400 mg sulfamethoxazole PO once daily. As an alternative, a dosage regimen of 160/800 mg PO three times per week may be used. Prophylaxis is recommended in HIV-infected patients with CD4 count less than 200 cells/mm3 or a history of AIDS-defining illness such as oropharyngeal candidiasis is present, CD4 percentage less than 14%, or CD4 count greater than 200 but less than 250 cells/mm3 if CD4 count monitoring every 3 months is not possible. Primary prophylaxis for pneumocystis infection may be discontinued if the CD4 count is greater than or equal to 200 cells/mm3 for at least 3 months. Prophylaxis should be restarted if CD4 count is less than 200 cells/mm3. If PCP is diagnosed or recurs at a CD4 count of greater than or equal to 200 cells/mm3, prophylaxis is lifelong.

    Infants >= 1 month and Children

    150 mg/m2 trimethoprim; 750 mg/m2 sulfamethoxazole PO per day in two divided doses for 3 consecutive days each week. Acceptable alternative regimens include 150 mg/m2 trimethoprim; 750 mg/m2 sulfamethoxazole PO once daily for 3 consecutive days each week, or 150 mg/m2 trimethoprim; 750 mg/m2 sulfamethoxazole PO per day in two divided doses given three times per week on alternate days (e.g., Monday, Wednesday, Friday), or 150 mg/m2 trimethoprim; 750 mg/m2 sulfamethoxazole PO per day in two divided doses given every day (Max: 320 mg trimethoprim; 1600 mg sulfamethoxazole/day). Prophylaxis is recommended for HIV-exposed (indeterminate status) infants and all HIV-infected infants less than 12 months of age regardless of CD4 counts, children 1 to 5 years of age with CD4 < 15% or CD4 count < 500 cells/mm3, and children 6 to 12 years of age with CD4 less than 15% or CD4 count less than 200 cells/mm3. It is recommended that infants born to HIV-infected women be considered for prophylaxis beginning at 4 to 6 weeks of age. Discontinue prophylaxis in children who are subsequently HIV-negative. HIV-infected infants and infants whose infection status remains unknown should continue to receive prophylaxis for the first year of life. For children 1—5 years of age, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy if  CD4 count is greater than 500 cells/mm3 or CD4 percentage is greater than or equal to 15% for more than 3 consecutive months. For children at least 6 years of age, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy if CD4 count is > 200 cells/mm3 or CD4 percentage is greater than or equal to 15% for more than 3 consecutive months. Primary prophylaxis should be restarted if CD4 count falls to less than 15% or CD4 count less than 500 cells/mm3 in children 1—5 years of age or less than 200 cells/mm3 in children greater than or equal to 6 years of age.

    For secondary PCP prophylaxis in HIV-infected patients.
    Oral dosage
    Adults and Adolescents

    160 mg trimethoprim; 800 mg sulfamethoxazole PO once daily or 80 mg trimethoprim; 400 mg sulfamethoxazole PO once daily. As an alternative, a dosage regimen of 160 mg trimethoprim ;800 mg sulfamethoxazole PO three times per week may be used. Secondary prophylaxis should be discontinued for those patients whose CD4 count is greater than or equal to 200 cells/mm3 for at least 3 months in response to highly active antiretroviral therapy. Prophylaxis should be restarted if the CD4 count decreases to less than 200 cells/mm3. If PCP is diagnosed or recurs at a CD4 count of greater than or equal to 200 cells/mm3, prophylaxis is lifelong.

    Infants >= 1 month and Children

    150 mg/m2 trimethoprim; 750 mg/m2 sulfamethoxazole per day PO in two divided doses for 3 consecutive days each week. Acceptable alternative regimens include 150 mg/m2 trimethoprim; 750 mg/m2 sulfamethoxazole PO once daily for 3 consecutive days each week, or 150 mg/m2 trimethoprim; 750 mg/m2 sulfamethoxazole PO per day in two divided doses given 3 times/week on alternate days (e.g., Monday, Wednesday, Friday), or 150 mg/m2 trimethoprim; 750 mg/m2 sulfamethoxazole per day PO in two divided doses given every day (Max: 320 mg trimethoprim; 1600 mg sulfamethoxazole/day).

    For children 1—5 years of age, secondary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy and their CD4 count is > 500 cells/mm3 or CD4 percentage is > 15% for more than 3 consecutive months. For children at least 6 years of age, secondary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy and their CD4 count is > 200 cells/mm3 or CD4 percentage is > 15% for more than 3 consecutive months.

    For primary PCP prophylaxis in immunocompromised patients with primary immunodeficiency disease (especially severe combined immunodeficiency disease), lymphoreticular malignancies (especially acute lymphatic leukemia and human T-cell lymphotropic virus-associated leukemia or lymphoma), organ transplantation (especially lung or heart-lung), and solid tumors, particularly brain tumors.
    Oral dosage
    Adults

    160 mg trimethoprim; 800 mg sulfamethoxazole PO once daily. Alternative regimens include 80; 400 mg PO once daily and 160; 800 mg PO three times per week. Larger dosages (e.g., 320 mg trimethoprim; 800 mg sulfamethoxazole PO per day) are sometimes used for prophylaxis of urinary tract and other infections, in addition to Pneumocystis carinii infection prophylaxis.

    For primary PCP prophylaxis in recipients of bone marrow allografts.
    Oral dosage
    Adults

    Trimethoprim 320 mg; sulfamethoxazole 1600 mg per day PO given only twice weekly beginning on day of marrow engraftment and continuing for 180 days or for the duration of immunosuppressive therapy has been recommended. Oral TMP-SMX has been administered in various dosage regimens from as infrequently as twice weekly, to as frequently as daily, in recipients of bone marrow allografts.

    Oral dosage
    Adults

    160 mg trimethoprim; 800 mg sulfamethoxazole PO once daily.

    Infants >= 2 months, Children, and Adolescents

    150 mg/m2 trimethoprim; 750 mg/m2 sulfamethoxazole PO per day in 2 divided doses for 3 consecutive days each week (Max dose: 320 mg trimethoprim; 1600 mg sulfamethoxazole/day).

    For the treatment of otitis media due to susceptible strains of Haemophilus influenzae or Streptococcus pneumoniae.
    For otitis media with otorrhea due to community-acquired methicillin-resistant Staphylococcus aureus†.
    Oral dosage
    Infants and Children

    A retrospective study reported the use of SMX-TMP plus topical antimicrobials for treating acute otitis media unresponsive to oral antibiotics and/or fluoroquinolone ear drops. Six children with culture-positive MRSA received 8 mg/kg/day (trimethoprim component) in 2 divided doses, given every 12 hours, plus a topical antimicrobial agent (e.g., gentamicin sulfate or polymyxin B; neomycin; hydrocortisone [Cortisporin]) for 10—14 days. All six cases resolved with treatment.

    Oral dosage
    Adults†

    160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours.

    Infants >= 2 months, Children, and Adolescents

    The manufacturer recommends 8 mg/kg/day trimethoprim component PO and 40 mg/kg/day sulfamethoxazole component in 2 divided doses given every 12 hours x10 days (Max: 160 mg trimethoprim/800 mg sulfamethoxazole per dose). The American Academy of Pediatrics recommends 6—10 mg/kg/day (trimethoprim component) PO in 2 divided doses. NOTE: Trimethoprim/sulfamethoxazole is not recommended as second-line therapy for children who have failed amoxicillin therapy. Alternatively, the manufacturer recommends administering the following doses PO every 12 hours: for patients >= 40 kg, 1 DS tablet (160 mg trimethoprim/800 mg sulfamethoxazole), 2 SS tablets (80 mg trimethoprim/400 mg sulfamethoxazole per tablet) or 20 ml of the suspension; for patients >= 30 kg and < 40 kg, 1.5 SS tablets or 15 ml of the suspension; for patients >= 20 kg and < 30 kg, 1 SS tablet or 10 ml of the suspension; for patients >= 10 kg and < 20 kg, 5 ml of the suspension.

    Intravenous dosage†
    Adults, Adolescents, Children, and Infants > 2 months

    8—10 mg/kg/day (trimethoprim component) IV in 2—4 equally divided doses.

    For the treatment of acute exacerbations of chronic bronchitis.
    Oral dosage
    Adults

    The manufacturer recommends 160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 14 days.

    For the treatment of gastroenteritis, infectious diarrhea, and gastrointestinal infections.
    For the treatment of cholera† caused by Vibrio cholerae.
    Oral dosage
    Adults

    160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours.

    Children and Adolescents

    5 mg/kg/dose (trimethoprim component) PO every 12 hours.

    Intravenous dosage
    Adults

    8 to 10 mg/kg/day (trimethoprim component) IV in 2 to 4 equally divided doses.

    Infants 2 months and older, Children, and Adolescents

    8 to 10 mg/kg/day (trimethoprim component) IV in 2 to 4 equally divided doses. Do not exceed 15 to 20 mg/kg/day of trimethoprim.

    For the treatment of cyclosporiasis† due to Cyclospora cayetanensis.
    Oral dosage
    Adults

    160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 7 days. A higher dose (160 mg (trimethoprim component) PO 4 times daily for 10 days) has been used in HIV patients. Diarrhea and abdominal pain stopped in all patients in an average of 2.5 days. Maintenance of remission was accomplished with 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times weekly.

    Children and Adolescents

    5 mg/kg/dose (trimethoprim component) PO every 12 hours for 7 days.

    For the treatment of shigellosis.
    Oral dosage
    Adults

    160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 5 days. The HIV guidelines recommend treating for 7 to 10 days or extend therapy to at least 14 days with bacteremia. Recurrent infection may require treating for up to 6 weeks. Shigella infections that are acquired outside of the U.S. may have high rates of trimethoprim; sulfamethoxazole resistance.

    Adolescents

    7.5 to 8 mg/kg/day trimethoprim component PO in 2 divided doses, given every 12 hours. Alternatively, the manufacturer recommends administering the following doses PO every 12 hours: for patients weighing 40 kg or more, 1 DS tablet (160 mg trimethoprim/800 mg sulfamethoxazole), 2 SS tablets (80 mg trimethoprim/400 mg sulfamethoxazole per tablet) or 20 ml of the suspension; for patients weighing 30 kg or more and less than 40 kg, 1.5 SS tablets or 15 mL of the suspension; for patients weighing 20 kg or more and less than 30 kg, 1 SS tablet or 10 mL of the suspension; for patients weighing 10 kg or more and less than 20 kg, 5 mL of the suspension. 160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours is recommended by the HIV guidelines. Treat for 7 to 10 days or extend therapy to at least 14 days with bacteremia. Recurrent infection may require treating for up to 6 weeks. Shigella infections that are acquired outside of the U.S. may have high rates of trimethoprim; sulfamethoxazole resistance.

    Infants and Children 2 months and older

    7.5 to 8 mg/kg/day trimethoprim component PO in 2 divided doses, given every 12 hours. Alternatively, the manufacturer recommends administering the following doses PO every 12 hours: for patients weighing 40 kg or more, 1 DS tablet (160 mg trimethoprim/800 mg sulfamethoxazole), 2 SS tablets (80 mg trimethoprim/400 mg sulfamethoxazole per tablet) or 20 mL of the suspension; for patients weighing 30 kg or more and less than 40 kg, 1.5 SS tablets or 15 mL of the suspension; for patients weighing 20 kg or more and less than 30 kg, 1 SS tablet or 10 mL of the suspension; for patients weighing 10 kg or more and less than 20 kg, 5 mL of the suspension.

    Intravenous dosage
    Adults and Adolescents

    8 to 10 mg/kg/day (trimethoprim component) IV in 2 to 4 equally divided doses for 5 days. 160 mg trimethoprim/800 mg sulfamethoxazole IV every 12 hours is recommended by the HIV guidelines. Treat for 7 to 10 days or extend therapy to at least 14 days with bacteremia. Recurrent infection may require treating for up to 6 weeks. Shigella infections that are acquired outside of the U.S. may have high rates of trimethoprim; sulfamethoxazole resistance.

    Infants and Children 2 months and older

    8 to 10 mg/kg/day (trimethoprim component) IV in 2 to 4 equally divided doses for 5 days.

    For the treatment of traveler's diarrhea due to enterotoxigenic Escherichia coli.
    Oral dosage
    Adults

    160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 5 days.

    For traveler's diarrhea prophylaxis†.
    Oral dosage
    Adults

    160 mg trimethoprim/800 mg sulfamethoxazole PO per once daily for the duration of the period at risk (up to 3 weeks) and continue for 1 to 2 days after returning home.

    For the treatment of isosporiasis† in HIV-positive patients.
    Oral or Intravenous dosage
    Adults and Adolescents

    160 mg trimethoprim/800 mg sulfamethoxazole PO or IV 4 times daily for 10 days is recommended by the HIV guidelines. Alternatively, 160 mg trimethoprim/800 mg sulfamethoxazole PO or IV every 12 hours for 7 to 10 days can be administered. Dose and duration may be increased (up to 3 to 4 weeks) if symptoms worsen or persist. After initial treatment, chronic maintenance therapy (secondary prophylaxis) should continue until CD4 count is 200 cells/mm3 or more for at least 6 months after antiretroviral therapy has been initiated and there is no further evidence of I. belli infection.

    For chronic maintenance therapy (secondary prophylaxis) of isosporiasis† in HIV-positive patients.
    Oral dosage
    Adults and Adolescents

    160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times weekly is recommended by the HIV guidelines. Alternatively, doses of 160 mg trimethoprim/800 mg sulfamethoxazole PO daily or 320 mg trimethoprim/1600 mg sulfamethoxazole PO 3 times weekly can be administered. Secondary prophylaxis should continue until CD4 count is 200 CD4 cells/mm3 or more for at least 6 months after antiretroviral therapy has been initiated and there is no further evidence of I. belli infection.

    For the treatment of salmonellosis† in HIV-infected patients.
    Intravenous and Oral dosage
    Adults and Adolescents

    160 mg trimethoprim/800 mg sulfamethoxazole PO or IV every 12 hours is recommended as an alternative therapy to a quinolone in the HIV guidelines. For patients with CD4 count of 200 cells/mm3, or more, the duration of therapy is 7 to 14 days for patients without bacteremia and 14 days for patients with bacteremia. A longer duration may be necessary with persistent or complicated infections. For patients with CD4 count less than 200 cells/mm3, the duration of therapy is 2 to 6 weeks with or without bacteremia. The role of long term secondary prophylaxis is not well established, but may be considered for patients with recurrent infection and in patients with CD4 count less than 200 cells/mm3 with severe diarrhea.

    For urinary tract infection (UTI) prophylaxis†.
    Oral dosage
    Adults

    40—80 mg (trimethoprim component) PO once daily each day or three times a week.

    Infants >= 2 months, Children, and Adolescents

    2 mg/kg (trimethoprim component) PO once daily in the evening or 5 mg/kg (trimethoprim component) PO twice per week have been used. In addition, 2 mg/kg (trimethoprim component) PO daily was evaluated in a 12-month, randomized, placebo-controlled trial. Pediatric patients (n = 564, median age = 14 months) with recurrent urinary tract infections (UTIs) were included; there was a 7% reduction in the absolute risk of symptomatic UTIs in predisposed children. The pattern of recurrence suggested that the greatest benefit of prophylaxis came during the first 6 months, which was the most likely time for recurrent infection. However, the data suggest that prolonged administration resulted in changes in bacterial susceptibility patterns that increased the risk of symptomatic UTI with bacteria resistant to sulfamethoxazole; trimethoprim.

    For bacterial infection prophylaxis† in HIV-infected children and infants.
    For secondary prophylaxis† in HIV-infected children and infants with > 2 invasive bacterial infections in a 1-year period.
    Oral dosage
    Infants and Children

    The Centers for Disease Control (CDC) mainly recommends prophylaxis only in children at risk for other opportunistic infections (i.e. Pneumocystis pneumonia). Previously, the CDC recommended 150 mg/m2/day (trimethoprim component) PO given in two divided doses.

    For primary prophylaxis† to reduce opportunistic infection in HIV-infected children (regardless of CD4 count).
    Oral dosage
    Infants and Children

    A randomized double-blind placebo-controlled study in Zambian children aged 1—14 years (n=541) with clinical features of HIV-infection was done. The study evaluated the efficacy of SMX-TMP in reducing opportunistic infections in an area with high-levels of in vitro bacterial resistance to SMX-TMP. Children < 5 years received 240 mg (5 ml of suspension) PO daily and those >= 5 years received SMX-TMP 480 mg (10 ml suspension) PO daily, or matching placebo. SMX-TMP reduced mortality by 43% and hospitalization by 23% compared to placebo. It was concluded that children of all ages with clinical features of HIV infection receive SMX-TMP prophylaxis in resource-poor areas, regardless of local resistance to the antibiotic. The CDC does not recommend primary prophylaxis of bacterial infections when Pneumocystis pneumonia prophylaxis is not warranted.

    As an alternative therapy for the treatment of toxoplasmic encephalitis† (TE) due to Toxoplasma gondii.
    Oral or Intravenous dosage
    Adults and Adolescents

    The HIV guidelines recommend a dose of 5 mg/kg (trimethoprim component) PO or IV twice daily as an alternative regimen. If pyrimethamine is unavailable or with a delay in availability, sulfamethoxazole; trimethoprim (SMX-TMP) should be utilized. For patients with a sulfa allergy, desensitization should be attempted and atovaquone should be administered until therapeutic doses of SMX-TMP are achieved. 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.

    For toxoplasmosis prophylaxis†, specifically prevention of toxoplasmic encephalitis (TE) due to Toxoplasma gondii.
    For primary prophylaxis† in HIV-infected patients.
    Oral dosage
    Adults and Adolescents

    The HIV guidelines recommend a dose of 160 mg trimethoprim; 800 mg sulfamethoxazole PO once daily in patients with an IgG antibody to Toxoplasma and a CD4+ count less than 100 cells/mm3. As an alternative, a dosage regimen of 160 mg trimethoprim; 800 mg sulfamethoxazole PO three times per week or 80 mg trimethoprim; 400 mg sulfamethoxazole daily may be used. Primary prophylaxis for TE may be discontinued in patients who have responded to highly active antiretroviral therapy with an increase in CD4 counts to greater than 200 cells/mm3 for at least 3 months. Prophylaxis should be reintroduced if the CD4 counts decrease to less than 100—200 cells/mm3.

    Infants >= 2 months and Children

    150 mg/m2 trimethoprim; 750 mg/m2 sulfamethoxazole per day PO in two divided doses (Max: 320 mg trimethoprim; 1600 mg sulfamethoxazole/day) for infants and children < 6 years of age with a CD4 percentage < 15% or children > 6 years of age with a CD4 count < 100 cells/mm3. Acceptable alternative regimens include 150 mg/m2 trimethoprim; 750 mg/m2 sulfamethoxazole PO once daily for 3 consecutive days each week or 150 mg/m2 trimethoprim; 750 mg/m2 sulfamethoxazole PO per day in two divided doses given three times per week on alternate days (e.g., Monday, Wednesday, Friday). Prophylaxis should not be discontinued in infants < 1 year of age. For children 1—5 years of age, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy if CD4 percentage is >= 15% for more than 3 consecutive months. For children at least 6 years of age, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy if CD4 count is > 100—200 cells/mm3 or CD4 percentage is >= 15% for more than 3 consecutive months.

    For chronic maintenance therapy† (secondary prophylaxis†) after acute toxoplasmosis infection.
    Oral dosage
    Adults and Adolescents

    160 mg trimethoprim; 800 mg sulfamethoxazole PO twice daily or once daily is recommended as an alternative in the HIV guidelines. Once daily therapy may be associated with an increased risk of relapse; therefore, a gradual transition from acute therapy may be beneficial, utilizing the twice daily dose for 4 to 6 weeks before switching to once daily dosing. Chronic maintenance therapy may be discontinued if initial therapy is successfully completed, patients remain free of signs and symptoms of encephalitis, and have a CD4 count greater than 200 cells/mm3 for more than 6 months. Restart chronic maintenance therapy if the CD4 count drops below 200 cells/mm3.

    For the treatment of Legionnaire's disease† caused by Legionella pneumophila.
    Intravenous dosage
    Adults

    160 mg trimethoprim/800 mg sulfamethoxazole IV every 8 hours.

    Oral dosage
    Adults

    160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours.

    For the treatment of actinomycotic mycetoma†.
    For actinomycotic mycetoma† caused by Actinomadura pelletierii, Actinomadura madurae, Streptomyces somaliensis.
    Oral dosage
    Adults

    23 mg/kg/day PO of sulfamethoxazole and 4.6 mg/kg/day of trimethoprim PO in two divided doses in combination with streptomycin.

    For actinomycotic mycetoma† caused by Nocardia brasiliensis, Nocardia asteroides, or Nocardia otitidiscaviarum.
    Oral dosage
    Adults

    45 mg/kg/day PO of sulfamethoxazole and 9 mg/kg/day of trimethoprim PO in two divided doses in combination with dapsone or amikacin.

    For the treatment of nocardiosis† caused by Nocardia sp..
    Oral dosage
    Adults

    Uncertainty exists regarding the dose of co-trimoxazole for this condition. A retrospective review of 19 patients at Duke University who received co-trimoxazole for treatment of documented Nocardia infection revealed that patients received an average of 8.2 regular strength tablets/day for an average of 7.2 months. Resolution was achieved in 17/19 patients and in 9/19, co-trimoxazole was the only form of therapy given.

    For the treatment of pertussis (whooping cough)† caused by Bordetella pertussis or for postexposure pertussis prophylaxis†.
    NOTE: For postexposure prophylaxis, administer to close contacts within 3 weeks of exposure, especially in high-risk patients (e.g., women in 3rd trimester, infants).
    Oral dosage
    Adults

    160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 14 days.

    Infants > 2 months and Children

    8 mg/kg/day trimethoprim/40 mg/kg/day sulfamethoxazole PO in 2 divided doses for 14 days.

    For the treatment of bacteremia† and catheter-associated infections†.
    Intravenous dosage
    Adults

    3 to 5 mg/kg/dose (trimethoprim component) IV every 8 hours for certain catheter-associated infections. In patients with persistent MRSA bacteremia and vancomycin treatment failures, 5 mg/kg/dose (trimethoprim component) IV every 12 hours in combination with high dose daptomycin. If there is reduced susceptibility to vancomycin and daptomycin, sulfamethoxazole; trimethoprim may be administered as a single agent or in combination with other antibiotics.

    Infants 2 months and older, Children, and Adolescents

    6 to 12 mg/kg/day (trimethoprim component) IV divided every 12 hours for mild-to-moderate infections and 15 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 8 hours for certain serious catheter-associated infections.

    For prevention of bacteremia† (i.e., bacteremia prophylaxis†) or spontaneous bacterial peritonitis† (i.e., peritonitis prophylaxis†) in patients with cirrhosis and ascites.
    Oral dosage
    Adults

    Sixty patients with cirrhosis and ascites were randomly assigned to receive 1 SMX-TMP double-strength tablet PO once daily (i.e., 160 mg trimethoprim/800 mg sulfamethoxazole) for 5 consecutive days each week for 3 months or no treatment. The incidence of spontaneous bacterial peritonitis or bacteremia was significantly less in the group that received oral therapy with SMX-TMP.

    For the treatment of typhoid fever† due to Salmonella typhi.
    For acute infections.
    Oral and Intravenous dosage
    Adults, Adolescents, and Children

    8 mg/kg/day (trimethoprim component) PO/IV in divided doses for 14 days.

    For chronic carriers.
    Oral dosage
    Adults

    160—800 mg (trimethoprim component) PO twice daily for 6 weeks.

    For the treatment of Staphylococcus aureus infections†, including endocarditis†.
    Intravenous dosage
    Adults

    In a prospective, randomized, double-blind trial, SMX-TMP dosed as 320 mg trimethoprim IV every 12 hours was compared to vancomycin in IV drug abusers with infections due to Staphylococcus aureus. Although the cure rate was significantly higher with vancomycin after roughly 3 weeks of therapy (e.g., 98% for vancomycin vs. 86% for SMX-TMP), the authors concluded that SMX-TMP could be considered an alternative in patients who cannot receive vancomycin if infection is due to methicillin-sensitive S. aureus. Clinical practice guidelines do not recommend SMX-TMP for endocarditis but acknowledge occasional use as salvage therapy.

    For the treatment of methicillin-resistant Staphylococcus aureus (MRSA) skin and skin structure infections†, including cellulitis†.
    Oral dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 1—2 DS tablets (160 mg trimethoprim and 800 mg sulfamethoxazole) PO every 12 hours for 5—10 days. 

    Infants > 2 months, Children, and Adolescents

    The Infectious Diseases Society of America (IDSA) recommends 4—6 mg/kg (trimethoprim component) PO every 12 hours for 5—10 days.

    For the treatment of granuloma inguinale† (Donovanosis) caused by Klebsiella granulomatis.
    Oral dosage
    Adults

    As an alternative, the CDC recommends 160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for a minimum of 3 weeks and until all lesions have completely healed. The addition of an aminoglycoside, such as gentamicin, should be considered if lesions do not respond within the first few days of therapy or if the patient also has HIV infection. For pregnant and lactating patients, use erythromycin or azithromycin.

    Adolescents

    The American Academy of Pediatrics (AAP) recommends 160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for a minimum of 3 weeks and until all lesions have completely healed.

    For the treatment of therapy-resistant pediculosis† capitis (head lice infestation) due to Pediculus capitis†.
    Oral dosage
    Adults

    Some studies suggest that SMX-TMP is effective. Typical dosage 5 mg/kg/dose (based on trimethoprim component) PO twice daily for 3 days and followed by another 3-day course after a 7—10 day interval.

    Children 2 to 13 years

    In one study, 115 children randomly received one of 3 treatment regimens: topical 1% permethrin alone; oral SMX-TMP 5 mg/kg/dose (based on the trimethoprim component) PO twice daily for 10 days; or the combination of topical 1% permethrin and oral SMX-TMP. At 2-week follow-up, the success rates were 79.5%, 83%, and 95%, respectively. At 4-weeks, the success rates were 72%, 78%, and 92.5%, respectively. Oral SMX-TMP either alone or combined with topical 1% permethrin was an effective alternative; however, it was recommended that combination therapy be reserved for cases of lice resistance or multiple treatment failures.

    For the treatment of melioidosis† and for postexposure prophylaxis.
    Oral dosage
    Adults weighing more than 60 kg

    320 mg trimethoprim/1,600 mg sulfamethoxazole PO every 12 hours for 12 weeks for the oral eradication-phase of therapy after initial IV treatment and for 21 days as postexposure prophylaxis during a public health emergency. Consider adding sulfamethoxazole; trimethoprim to carbapenem therapy in setting of persistent bacteremia.

    Adults weighing 40 to 60 kg

    240 mg trimethoprim/1,200 mg sulfamethoxazole PO every 12 hours for 12 weeks for the oral eradication-phase of therapy after initial IV treatment and for 21 days as postexposure prophylaxis during a public health emergency. Consider adding sulfamethoxazole; trimethoprim to carbapenem therapy in setting of persistent bacteremia.

    Adults weighing less than 40 kg

    160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours for 12 weeks for the oral eradication-phase of therapy after initial IV treatment and for 21 days as postexposure prophylaxis during a public health emergency. Consider adding sulfamethoxazole; trimethoprim to carbapenem therapy in setting of persistent bacteremia.

    Infants 2 months and older, Children, and Adolescents

    8 mg/kg/dose trimethoprim component and 40 mg/kg/dose sulfamethoxazole component PO (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole per dose) every 12 hours for 12 weeks for the oral eradication-phase of therapy after initial IV treatment and for 21 days as postexposure prophylaxis during a public health emergency. Consider adding sulfamethoxazole; trimethoprim to carbapenem therapy in setting of persistent bacteremia. May add to carbapenem therapy in setting of persistent bacteremia.

    For sulfonamide desensitization† in patients requiring sulfamethoxazole; trimethoprim therapy.
    Rapid sulfonamide desensitization† protocol.
    Oral dosage
    Adults

    This rapid protocol was studied in HIV infected patients who required SMX-TMP therapy. Increasing doses of SMX-TMP are given every 15 minutes for 31 doses; then, if protocol tolerated, begin sulfonamide therapy as indicated. The protocol is as follows:
    Doses 1—3 (10 ng/ml SMX-TMP): 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 0.00007 mg of the SMX component.
    Doses 4—7 (100 ng/ml SMX-TMP): 0.5 ml, 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 0.00075 mg of the SMX component.
    Doses 8—11 (1 mcg/ml SMX-TMP): 0.5 ml, 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 0.0075 mg of the SMX component.
    Doses 12—15 (10 mcg/ml SMX-TMP): 0.5 ml, 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 0.075 mg of the SMX component.
    Doses 16—19 (100 mcg/ml SMX-TMP): 0.5 ml, 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 0.75 mg of the SMX component.
    Doses 20—23 (1 mg/ml SMX-TMP): 0.5 ml, 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 7.5 mg of the SMX component.
    Doses 24—27 (10 mg/ml SMX-TMP): 0.5 ml, 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 75 mg of the SMX component.
    Doses 28—30 (40 mg/ml SMX-TMP): 2 ml, 4 ml, and 8 ml PO given 15 minutes apart for a total dose of 560 mg of the SMX component.
    Dose 31: 1 double strength tablet (800 mg of the SMX component) PO.

    Ambulatory sulfonamide desensitization† protocol.
    Oral dosage
    Adults

    This ambulatory desensitization protocol was studied in HIV infected patients who required SMX-TMP prophylaxis. Increasing doses of SMX-TMP given PO 3 times daily were used for 8 days. On the ninth day and if protocol tolerated, the patients received 1 double-strength tablet (800 mg/160mg SMX-TMP) PO once daily. The protocol is as follows:
    Day 1 (0.00002 mg/ml SMX-TMP): 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 0.00007 mg of the SMX component.
    Day 2 (0.0002 mg/ml SMX-TMP): 0.5 ml, 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 0.00075 mg of the SMX component.
    Day 3 (0.002 mg/ml SMX-TMP): 0.5 ml, 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 0.0075 mg of the SMX component.
    Day 4 (0.02 mg/ml SMX-TMP): 0.5 ml, 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 0.075 mg of the SMX component.
    Day 5 (0.2 mg/ml SMX-TMP): 0.5 ml, 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 0.75 mg of the SMX component.
    Day 6 (2 mg/ml SMX-TMP): 0.5 ml, 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 7.5 mg of the SMX component.
    Day 7 (20 mg/ml SMX-TMP): 0.5 ml, 1 ml, 2 ml, and 4 ml PO given 15 minutes apart for a total dose of 75 mg of the SMX component.
    Day 8 (40 mg/ml SMX-TMP): 2 ml, 4 ml, and 8 ml PO given 15 minutes apart for a total dose of 560 mg of the SMX component.
    Day 9: Give 1 double strength tablet (800 mg of the SMX component) PO.

    For the management of methicillin-resistant Staphylococcus aureus (MRSA)-associated bone and joint infections†, including osteomyelitis† and septic/infectious arthritis†, or an orthopedic device-related infection†.
    For the management of methicillin-resistant Staphylococcus aureus (MRSA)-associated osteomyelitis†.
    Oral and Intravenous dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 3.5—4 mg/kg (trimethoprim component) PO or IV every 8—12 hours plus rifampin 600 mg PO daily. A minimum duration of 8 weeks is recommended; however, an additional 1—3 months (or longer for chronic infection or if no debridement performed) of oral rifampin plus another MRSA agent such as sulfamethoxazole/trimethoprim, may be necessary.

    For the management of methicillin-resistant Staphylococcus aureus (MRSA)-associated septic arthritis†.
    Oral and Intravenous dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 3.5—4 mg/kg (trimethoprim component) PO or IV every 8—12 hours for 3—4 weeks.

    For the management of methicillin-resistant Staphylococcus aureus (MRSA)-associated prosthetic joint infections†.
    Oral and Intravenous dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 3.5—4 mg/kg PO or IV every 8—12 hours plus rifampin 600 mg PO daily or 300—450 mg PO q12h for 2 weeks in patients with early-onset (< 2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (<= 3 weeks) of symptoms and debridement (but device retention). Additional oral therapy (rifampin plus another MRSA agent, such as sulfamethoxazole; trimethoprim) should start after the completion of IV therapy and continue for 3 months for hip infections or for 6 months for knee infections.

    For the management of methicillin-resistant Staphylococcus aureus (MRSA)-associated spinal implant infections†.
    Oral and Intravenous dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 3.5—4 mg/kg PO or IV every 8—12 hours plus rifampin 600 mg PO daily or 300—450 mg PO q12h in patients with early-onset spinal implant infections (<= 30 days after surgery) or implants in an actively infected site. Prolonged oral therapy (rifampin plus another MRSA agent, such as sulfamethoxazole; trimethoprim) should follow parenteral therapy; however, the optimal duration of parenteral and/or oral therapy is unclear. Oral therapy should be continued until spine fusion has occurred. Long term oral suppressive therapy may be considered in select cases, especially if device removal is not possible.

    For surgical infection prophylaxis†.
    Oral dosage
    Adults

    160 mg trimethoprim/800 mg sulfamethoxazole PO as single dose 1 hour before transrectal biopsy of the prostate or 320 mg trimethoprim/1600 mg sulfamethoxazole PO as single dose 1 to 3 hours before transurethral resection of the prostate. No intraoperative redosing and a duration of prophylaxis less than 24 hours for most procedures are recommended by clinical practice guidelines. Clinical practice guidelines recommend sulfamethoxazole; trimethoprim for urologic procedures involving lower tract instrumentation with risk factors for infection, including transrectal prostate biopsy.

    For the treatment of CNS infections†, including meningitis†, brain abscess†, subdural empyema†, spinal epidural abscess†, and septic thrombosis of the cavernous or dural venous sinus†.
    Intravenous dosage
    Adults

    10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 2 weeks as an alternative therapy for bacterial meningitis caused by E. coli, L. monocytogenes, or or methicillin-resistant Staphylococcus aureus (MRSA). For other MRSA CNS infections, including brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus, 5 mg/kg IV every 8 to 12 hours for 4 to 6 weeks. Oral rifampin may be added.

    Infants 2 months and older, Children, and Adolescents

    10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours as an alternative therapy for bacterial meningitis caused by E. coli, L. monocytogenes, or methicillin-resistant Staphylococcus aureus. Treat for 2 weeks for meningitis and for 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, or septic thrombosis of the cavernous or dural venous sinus.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    20 mg/kg/day PO/IV (trimethoprim component).

    Elderly

    20 mg/kg/day PO/IV (trimethoprim component).

    Adolescents

    20 mg/kg/day PO/IV (trimethoprim component).

    Children

    20 mg/kg/day PO/IV (trimethoprim component).

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Both sulfamethoxazole and trimethoprim are metabolized by the liver. Dosage adjustments may be necessary in patients with hepatic impairment, however, specific dosage adjustment guidelines are not available.

    Renal Impairment

    CrCl >= 30 ml/min: No dosage adjustment needed. An alternative recommendation suggests giving the full daily dose divided every 12 hours (for example, 8—12 mg/kg/day of the trimethoprim component IV/PO divided every 12 hours) for 14 days, then giving half the daily dose administered every 24 hours (for example, 4—6 mg/kg/day of the trimethoprim component IV/PO once daily).
    CrCl 15—<30 ml/min: The manufacturer recommends to reduce the recommended dose by 50% (or extend dosing interval). An alternative general dosing recommendation suggests giving the full daily dose divided every 12 hours (for example, 8—12 mg/kg/day of the trimethoprim component IV/PO divided every 12 hours) for 24 to 48 hours, then giving half the daily dose administered every 24 hours (for example, 4—6 mg/kg/day of the trimethoprim component IV/PO once daily). For PCP treatment, 5 mg/kg of the trimethoprim component IV/PO every 6—8 hours for 48h, then 3.5—5 mg/kg IV/PO every 12 hours has been recommended.; an alternative regimen of 15—20 mg/kg/day of the trimethoprim component IV/PO divided every 6—8 hours for 48 hours, then 7—10 mg/kg/day IV/PO of the trimethoprim component divided every 12 hours has been suggested. For PCP prophylaxis, half the normal dose has been recommended.; a dose of 5 mg/kg of the trimethoprim component IV/PO administered every 24—48 hours for 3—7 doses per week has also been recommended.
    CrCl < 15 ml/min: Use not recommended by the manufacturer. An alternative general dosing recommendation suggests giving the normal full daily dose (for example, 8—12 mg/kg/dose of the trimethoprim component IV/PO) every 48 hours or half the daily dose administered daily in in 1—2 divided doses (for example 4—6 mg/kg/day of the trimethoprim component IV/PO divided every 12—24 hours). For PCP treatment, 7—10 mg/kg/day of the trimethoprim component IV/PO in 1—2 divided doses has been recommended by the CDC. Alternatively, 15—20 mg/kg/dose of the trimethoprim component IV/PO administered every 48 hours has been suggested. For PCP prophylaxis, half the normal dose or use of an alternative agent has been recommended.; a dose of 5 mg/kg IV/PO of the trimethoprim component administered every 48—72 hours has also been recommended.
     
    Intermittent hemodialysis
    The manufacturer recommends against use during hemodialysis. An alternative general dosing recommendation suggests giving the normal full daily dose (for example, 8—12 mg/kg of the trimethoprim component IV/PO) before dialysis and then giving half the normal daily dose (for example, 4—6 mg/kg of the trimethoprim component IV/PO) after dialysis. A pharmacokinetic study demonstrated that 44% of the administered trimethoprim and 57% of the administered sulfamethoxazole dose was removed during hemodialysis, suggesting that 50% of the normal dose be administered after the dialysis session. For PCP treatment, the CDC recommends administering 7—10 mg/kg of the trimethoprim component IV/PO after dialysis. Alternatively, 15—20 mg/kg/dose of the trimethoprim component IV/PO administered before dialysis with 7—10 mg/kg of the trimethoprim component IV/PO after dialysis has been recommended. For PCP prophylaxis, it is recommended to administer half the normal dose after each dialysis.; a dose of 5 mg/kg of the trimethoprim component IV/PO administered after each dialysis has also been recommended.
     
    Peritoneal dialysis
    Using the same dose as in patients with end-stage renal disease has been recommended; a pharmacokinetic study suggests that peritoneal dialysis does not substantially remove sulfamethoxazole; trimethoprim.
     
    Continuous renal replacement therapy
    Dosing of 2.5—7.5 mg/kg IV/PO of the trimethoprim component administered twice daily has been recommended for CVVH, CVVHD, and CVVHDF.

    ADMINISTRATION

     
    NOTE: The doses below are expressed in terms of the trimethoprim content of the fixed combination, which consists of 5 mg sulfamethoxazole: 1 mg trimethoprim.

    Oral Administration

    May be administered without regard to meals. Administer with food, water, or milk to minimize gastric irritation.

    Oral Liquid Formulations

    Suspension: Shake well before using.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Rapid or direct IV injection must be avoided.
    Dilute 5 ml of the concentrate for injection in 125 ml of D5W. For fluid-restricted patients, 75 ml of D5W may be used. Use diluted solution within 2 hours of preparation and do not refrigerate.
    If using Septra ADD-Vantage vials, dilute each 10 ml vial in ADD-Vantage diluent containers containing 250 ml of D5W.
    Infuse over a period of 60—90 minutes. Change infusion site every 48—72 hours.

    STORAGE

    Generic:
    - Discard unused portion 48 hours after initial puncture of container
    - Do not refrigerate reconstituted product
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Bacter-Aid DS :
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Bactrim:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Bactrim DS:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Septra:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Septra DS:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Sulfatrim:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Sulfatrim Pediatric:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Sultrex Pediatric :
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Carbonic anhydrase inhibitor hypersensitivity, sulfite hypersensitivity, sulfonamide hypersensitivity, sulfonylurea hypersensitivity, thiazide diuretic hypersensitivity, trimethoprim hypersensitivity

    Sulfamethoxazole; trimethoprim is contraindicated in patients with either sulfonamide hypersensitivity or trimethoprim hypersensitivity. Fatalities have been documented in patients with sulfonamide hypersensitivity who receive sulfonamides, usually secondary to Stevens-Johnson syndrome, toxic epidermal necrolysis, or hepatic necrosis. Because of structural similarity, sulfonamides should be used cautiously in patients with known allergic reactions to thiazide diuretics, oral sulfonylureas, or carbonic anhydrase inhibitors. Despite the chemical similarities between furosemide and sulfonamides and the logical conclusion that cross-sensitivity would occur, a thorough review of the published literature and direct communication with the manufacturer revealed no data supporting the conclusion that patients with sensitivity to sulfonamides also develop sensitivity to furosemide. Less is known regarding the cross-sensitivity between sulfonamides and the other agents, although some clinicians doubt that significant risk exists. Nevertheless, sulfamethoxazole; trimethoprim should be avoided in patients with furosemide hypersensitivity, thiazide diuretic hypersensitivity, sulfonylurea hypersensitivity, or carbonic anhydrase inhibitor hypersensitivity. Additionally, sulfamethoxazole; trimethoprim injection contains sodium metabisulfite and should not be used in patients with sulfite hypersensitivity; those at risk are found more frequently amongst asthmatic than non-asthmatic members of the population. Severe life-threatening anaphylactic reactions or less severe asthmatic episodes can develop in susceptible patients.

    Agranulocytosis, bone marrow suppression, folate deficiency, folate deficiency megaloblastic anemia, G6PD deficiency, hemolysis, thrombocytopenia

    Sulfamethoxazole; trimethoprim is contraindicated in patients with folate deficiency megaloblastic anemia since either component could exacerbate this condition; be use with caution in patients with mild folate deficiency. Sulfamethoxazole; trimethoprim is also contraindicated for use in patients with a history of trimethoprim and/or sulfonamide-induced immune thrombocytopenia. Thrombocytopenia may be immune-related and usually subsides within a week of treatment discontinuation; however, severe/life-threatening cases have been reported. Caution is advised when administering the drug to patients with bone marrow suppression, as sulfonamides have been associated with fatalities resulting from agranulocytosis, aplastic anemia, and other blood dyscrasias. Do not administer to patients with G6PD deficiency; hemolysis and hemolytic anemia may occur if patients with G6PD deficiency receive sulfamethoxazole; trimethoprim; this reaction is frequently dose related. Discontinue the drug at the first appearance of serious blood disorders.

    Hyperkalemia, hyponatremia, renal disease, renal failure, renal impairment

    Sulfamethoxazole; trimethoprim is contraindicated in patients with severe renal impairment, renal disease, or renal failure, defined as creatinine clearance (CrCl) less than 15 mL/minute, when renal function status cannot be monitored. It should be used cautiously in patients with moderate renal impairment (i.e., CrCl less than than 30 mL/minute); the dosage should be adjusted to avoid drug accumulation and potential toxicity. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in patients with preexisting risk factors (e.g., renal disease, elderly). Monitor serum potassium levels in patients with risk factors for developing drug-induced hyperkalemia (renal impairment, elderly, high-dose trimethoprim). In addition, use trimethoprim with caution in patients receiving drugs known to significantly increase serum potassium. Sulfamethoxazole; trimethoprim has also been associated with severe cases of hyponatremia, particularly in patients receiving treatment for pneumocystis pneumonia (PCP). Health care providers are advised to monitor for the development of hyponatremia and implement appropriate corrective measures as needed in symptomatic patients.

    Hepatic disease

    Sulfamethoxazole; trimethoprim is contraindicated in patients with marked hepatic damage or hepatic disease. Because both sulfonamides and trimethoprim are metabolized in the liver, caution should be used when these drugs are given to patients with any degree of hepatic disease. Metabolism can be decreased, and as a result, toxicity may occur. Patients who are "slow acetylators" may be more prone to idiosyncratic reactions to sulfonamides.

    Porphyria

    Sulfonamides, such as sulfamethoxazole, can cause an acute attack of porphyria, and should not be used in patients with this condition.

    Colitis, diarrhea, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis

    Almost all antibacterial agents have been associated with pseudomembranous colitis (antibiotic-associated colitis) which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may exist when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. It is known that systemic use of antibiotics predisposes patients to development of pseudomembranous colitis. Consideration should be given to the diagnosis of pseudomembranous colitis in patients presenting with diarrhea following sulfamethoxazole; trimethoprim administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. In milder cases, the colitis may respond to discontinuation of the offending agent. In moderate to severe cases, fluids and electrolytes, protein supplementation, and treatment with an antibacterial effective against Clostridium difficile may be warranted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over two months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken.

    Hypothyroidism

    As with all medications containing sulfonamides, use sulfamethoxazole; trimethoprim with caution in patients with hypothyroidism.

    Acquired immunodeficiency syndrome (AIDS)

    Caution is advised when administering sulfamethoxazole; trimethoprim to patients with acquired immunodeficiency syndrome (AIDS). Patient with AIDS may not tolerate or respond to treatment in the same manner as non-AIDS patients. Patients with AIDS may experience more drug-related side effects, including rash, fever, leukopenia, elevated hepatic enzymes, and hyperkalemia. Health care providers are encouraged to reevaluate sulfamethoxazole; trimethoprim therapy in patients who develop rash or other treatment-related adverse reactions. If treatment is continued, closely monitor potassium concentrations and ensure adequate fluid intake during therapy. Additionally, clinicians are advised to avoid coadministration of sulfamethoxazole; trimethoprim with leucovorin in HIV/AIDS patients for the treatment of pneumocystis pneumonia (PCP). During a clinical trials, HIV-positive patients with pneumocystis pneumonia who receiving these drugs in combination experienced treatment failure and excess mortality.

    Infants, neonates

    Sulfamethoxazole; trimethoprim is contraindicated in neonates and infants less than 2 months old. Sulfonamides may cause bilirubin displacement and kernicterus in this age group. Additionally, sulfamethoxazole; trimethoprim injection contains benzyl alcohol as a preservative. There have been reports of fatal gasping syndrome in neonates (less than 1 month of age) after the administration of parenteral solutions containing the preservative benzyl alcohol at dosages of 99 mg/kg/day or more. Normal sulfamethoxazole; trimethoprim doses would deliver benzyl alcohol at amounts lower than those reported with gasping syndrome; however, the minimum amount of benzyl alcohol to cause toxicity is unknown. Consider the combined daily metabolic load of benzyl alcohol from all sources if using sulfamethoxazole; trimethoprim injection in infants. Sulfamethoxazole; trimethoprim may be used as adjunctive therapy with pyrimethamine in the treatment of congenital toxoplasmosis or for the prophylaxis of PCP in infants (1 month and older).

    Pregnancy

    Sulfamethoxazole; trimethoprim may cause fetal harm if administered during pregnancy. Use sulfamethoxazole; trimethoprim during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data have linked first trimester exposure to sulfamethoxazole; trimethoprim to an increased risk for congenital malformations (i.e., cardiovascular malformations, neural tube defects, oral cleft, urinary tract defects, club foot). In addition, sulfonamides are considered by some experts to be higher risk when used near term due to the potential for jaundice, hemolytic anemia, and kernicterus in the newborn; sulfonamides readily cross the placenta with fetal concentrations averaging 70% to 90% of maternal concentrations. 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. If sulfamethoxazole; trimethoprim is used during pregnancy, the patient should be advised of the potential risk to the fetus and supplemental multivitamins should be administered. Use of the drug is recommended for prophylaxis of pneumocystis pneumonia (PCP) in HIV-infected pregnant women.

    Breast-feeding

    Both sulfamethoxazole and trimethoprim are excreted into human breast milk at concentrations of approximately 2% to 5% of the recommended daily dose for infants over 2 months of age. Because of the potential risk of bilirubin displacement and kernicterus, avoid breast-feeding during treatment with sulfamethoxazole; trimethoprim. However, previous American Academy of Pediatrics (AAP) recommendations considered sulfamethoxazole; trimethoprim as usually compatible with breast-feeding. An extensive review in HIV-infected women suggested that the risk of kernicterus in the breast-feeding infant is very low. In a study of 12 newborn infants of less than 3 days postnatal age receiving systemic sulfamethoxazole; trimethoprim, the authors noted that despite therapeutic serum concentrations, there was no displacement of bilirubin from albumin in the newborns. If sulfamethoxazole; trimethoprim is administered to the mother of a young infant, monitor the infant for signs of increased bilirubin and jaundice. Ciprofloxacin, amoxicillin, and nitrofurantoin (cautioned in the infant with glucose-6-phosphate dehydrogenase deficiency) may be potential alternatives to consider during breast-feeding as generally considered compatible by previous AAP recommendations.

    Antimicrobial resistance, viral infection

    Sulfamethoxazole; trimethoprim will not effectively treat an established group A beta-hemolytic streptococcal infection; therefore, its use in patients with such infections should be avoided. Additionally the drug will not treat viral infection (e.g., common cold). Prescribing this drug in the absence of a proven, or strongly suspected, susceptible bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria (antimicrobial resistance). Patients should be told to complete the full course of treatment, even if they feel better earlier. Antibiotic therapy can result in superinfection or suprainfection with nonsusceptible organisms. Patients should be monitored closely.

    Hypoglycemia, malnutrition

    Cases of hypoglycemia have been reported in non-diabetic patients receiving treatment with sulfamethoxazole; trimethoprim. These events are uncommon and usually develop after a few days of therapy. Risk factors include, renal and hepatic dysfunction, malnutrition, and those patients receiving high drug doses.

    Sunlight (UV) exposure

    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 sulfamethoxazole; trimethoprim use at the first sign of erythema.

    Alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, coronary artery disease, diabetes mellitus, females, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, myocardial infarction, QT prolongation, thyroid disease

    Cases of QT prolongation resulting in ventricular tachycardia and torsade de pointes have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Use sulfamethoxazole; trimethoprim with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic disease may also be at increased risk for QT prolongation.

    Geriatric

    Sulfamethoxazole; trimethoprim is renally eliminated and should be used cautiously in geriatric patients, who have an age-related decline in renal function. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in patients with preexisting risk factors, such as geriatric patients. Monitor serum potassium levels in geriatric patients and use sulfamethoxazole; trimethoprim with caution in geriatric patients receiving drugs known to significantly increase serum potassium. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

    ADVERSE REACTIONS

    Severe

    erythema multiforme / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    periarteritis / Delayed / Incidence not known
    thrombotic thrombocytopenic purpura (TTP) / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    hepatic necrosis / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    vasculitis / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    myocarditis / Delayed / Incidence not known
    serum sickness / Delayed / Incidence not known
    megaloblastic anemia / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    erythema nodosum / Delayed / Incidence not known
    methemoglobinemia / Early / Incidence not known
    renal tubular necrosis / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    anuria / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known
    interstitial nephritis / Delayed / Incidence not known
    oliguria / Early / Incidence not known
    hyperkalemia / Delayed / Incidence not known
    aseptic meningitis / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    torsade de pointes / Rapid / Incidence not known
    uveitis / Delayed / Incidence not known

    Moderate

    leukopenia / Delayed / Incidence not known
    bullous rash / Early / Incidence not known
    neutropenia / Delayed / Incidence not known
    hypoprothrombinemia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    dysuria / Early / Incidence not known
    crystalluria / Delayed / Incidence not known
    neuritis / Delayed / Incidence not known
    hallucinations / Early / Incidence not known
    ataxia / Delayed / Incidence not known
    depression / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    stomatitis / Delayed / Incidence not known
    glossitis / Early / Incidence not known
    jaundice / Delayed / Incidence not known
    hypoglycemia / Early / Incidence not known
    phlebitis / Rapid / Incidence not known
    hyponatremia / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known

    Mild

    purpura / Delayed / Incidence not known
    cough / Delayed / Incidence not known
    maculopapular rash / Early / Incidence not known
    urticaria / Rapid / Incidence not known
    fever / Early / Incidence not known
    chills / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    rash (unspecified) / Early / Incidence not known
    photosensitivity / Delayed / Incidence not known
    vertigo / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    headache / Early / Incidence not known
    insomnia / Early / Incidence not known
    fatigue / Early / Incidence not known
    arthralgia / Delayed / Incidence not known
    weakness / Early / Incidence not known
    myalgia / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    vomiting / Early / Incidence not known
    abdominal pain / Early / Incidence not known
    diarrhea / Early / Incidence not known
    nausea / Early / Incidence not known
    diuresis / Early / Incidence not known
    injection site reaction / Rapid / Incidence not known

    DRUG INTERACTIONS

    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. (Moderate) Concomitant use of trimethoprim and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
    Acarbose: (Moderate) Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Therefore, a pharmacodynamic interaction leading to an increased risk of hypoglycemia may occur in patients taking antidiabetic agents and 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; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as sulfonamides. An enhanced effect of the displaced drug may occur.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (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.
    Acetohexamide: (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. Also, taking these drugs together may increase risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas
    Albiglutide: (Moderate) Sulfonamides may enhance the hypoglycemic action of incretin mimetics and other antidiabetic agents. 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. Patients should be closely monitored for this potential pharmacodynamic interaction while receiving any of these drugs in combination with incretin mimetics.
    Albuterol: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Albuterol; Ipratropium: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Alfuzosin: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include alfuzosin.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Aliskiren; Valsartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Alogliptin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Alogliptin; Metformin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Alogliptin; Pioglitazone: (Moderate) It is possible that an increase in the exposure of pioglitazone may occur when coadministered with other drugs that inhibit CYP2C8 such as trimethoprim. Monitor for changes in glycemic control if trimethoprim is coadministered with pioglitazone. (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Alpha-glucosidase Inhibitors: (Moderate) Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Therefore, a pharmacodynamic interaction leading to an increased risk of hypoglycemia may occur in patients taking antidiabetic agents and sulfonamides.
    Amantadine: (Major) Avoid the concomitant use of trimethoprim and amantadine as coadministration may result in increased serum concentrations of amantadine. Amantadine is an OCT2 substrate; trimethoprim is an inhibitor of this drug transporter. A single case of toxic delirium has been reported in the literature after coadministration of trimethoprim and amantadine. Monitor the patient for mental status changes if coadministration is necessary.
    Amiloride: (Major) Trimethoprim has a potassium-sparing effect and may induce hyperkalemia, especially in patients with pre-existing risk factors for hyperkalemia (e.g., renal disease). Patients, especially those with renal dysfunction, should be carefully monitored for hyperkalemia during concomitant use of potassium-sparing diuretics and trimethoprim.
    Amiloride; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Major) Trimethoprim has a potassium-sparing effect and may induce hyperkalemia, especially in patients with pre-existing risk factors for hyperkalemia (e.g., renal disease). Patients, especially those with renal dysfunction, should be carefully monitored for hyperkalemia during concomitant use of potassium-sparing diuretics and trimethoprim.
    Aminobenzoate Potassium: (Moderate) Aminobenzoate potassium should not be administered to patients taking sulfonamides or aminosalicylate sodium, aminosalicylic acid. Bacteria preferentially absorb aminobenzoate potassium instead of the antibacterial agents, decreasing their efficacy.
    Aminosalicylate sodium, Aminosalicylic acid: (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.
    Amiodarone: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include amiodarone.
    Amitriptyline: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include tricyclic antidepressants.
    Amitriptyline; Chlordiazepoxide: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include tricyclic antidepressants.
    Amlodipine; Benazepril: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Amlodipine; Olmesartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Amlodipine; Telmisartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Amlodipine; Valsartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include clarithromycin.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include clarithromycin.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with anagrelide include sulfamethoxazole; trimethoprim.
    Angiotensin II receptor antagonists: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Angiotensin-converting enzyme inhibitors: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Anthracyclines: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, or idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Apomorphine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include apomorphine.
    Aprepitant, Fosaprepitant: (Minor) Use caution if sulfamethoxazole and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of sulfamethoxazole. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Sulfamethoxazole is a CYP2C9 substrate and aprepitant is a CYP2C9 inducer. Administration of a CYP2C9 substrate, tolbutamide, on days 1, 4, 8, and 15 with a 3-day regimen of oral aprepitant (125 mg/80 mg/80 mg) decreased the tolbutamide AUC by 23% on day 4, 28% on day 8, and 15% on day 15. The AUC of tolbutamide was decreased by 8% on day 2, 16% on day 4, 15% on day 8, and 10% on day 15 when given prior to oral administration of aprepitant 40 mg on day 1, and on days 2, 4, 8, and 15. The effects of aprepitant on tolbutamide were not considered significant. When a 3-day regimen of aprepitant (125 mg/80 mg/80 mg) given to healthy patients on stabilized chronic warfarin therapy (another CYP2C9 substrate), a 34% decrease in S-warfarin trough concentrations was noted, accompanied by a 14% decrease in the INR at five days after completion of aprepitant.
    Arformoterol: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Aripiprazole: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include aripiprazole.
    Arsenic Trioxide: (Major) Avoid coadministration of sulfamethoxazole; trimethoprim and arsenic trioxide. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. QT prolongation should be expected with the administration of arsenic trioxide.
    Artemether; Lumefantrine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include artemether.
    Asenapine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include asenapine.
    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; Butalbital; 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.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (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: (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; 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.
    Aspirin, ASA; Pravastatin: (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.
    Atenolol; Chlorthalidone: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Atomoxetine: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include atomoxetine. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of TdP.
    Atovaquone: (Moderate) Concomitant administration of atovaquone with an oral combination of trimethoprim and sulfamethoxazole lead to a minor decreases in TMP and SMX AUCs by 16% and 10%, respectively, in a small number of HIV-positive subjects. No difference was observed in atovaquone pharmacokinetics. The effect of the interaction of atovaquone with TMP-SMX is minor and unlikely to be of clinical significance. (Moderate) Concomitant administration of atovaquone with an oral combination of trimethoprim and sulfamethoxazole lead to a minor decreases in TMP and SMX AUCs in a small number of HIV-positive subjects. This may not be of any clinical significance but should be used with caution.
    Atovaquone; Proguanil: (Moderate) Concomitant administration of atovaquone with an oral combination of trimethoprim and sulfamethoxazole lead to a minor decreases in TMP and SMX AUCs by 16% and 10%, respectively, in a small number of HIV-positive subjects. No difference was observed in atovaquone pharmacokinetics. The effect of the interaction of atovaquone with TMP-SMX is minor and unlikely to be of clinical significance. (Moderate) Concomitant administration of atovaquone with an oral combination of trimethoprim and sulfamethoxazole lead to a minor decreases in TMP and SMX AUCs in a small number of HIV-positive subjects. This may not be of any clinical significance but should be used with caution.
    Atropine; 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.
    Azathioprine: (Moderate) Azathioprine may interact with other drugs that are myelosuppressive. Drugs that may affect the production of leukocytes, including sulfamethoxazole; trimethoprim, SMX-TMP, may lead to exaggerated leukopenia, especially in patients who have received a renal transplant.
    Azelaic Acid; Copper; Folic Acid; Nicotinamide; Pyridoxine; Zinc: (Minor) Folate antagonists, such as trimethoprim, especially when used in high doses or over a prolonged period, inhibit dihydrofolate reductase and thus may inhibit the action of folic acid, vitamin B9. (Minor) L-methylfolate and trimethoprim should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with trimethoprim. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Azilsartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Azilsartan; Chlorthalidone: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Azithromycin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and sulfamethoxazole; trimethoprim should be used together cautiously. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim. In addition, there have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Concurrent use may increase the risk of QT prolongation.
    Bedaquiline: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include bedaquiline.
    Benazepril: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Benazepril; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Bendroflumethiazide; Nadolol: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    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.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole; therefore, it should be used cautiously when adminstered with sulfamethoxazole; trimethoprim, which has a possible risk for QT prolongation and TdP. Also, medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Intravenous sulfamethoxazole; trimethoprim, SMX-TMP contains ethanol. A disulfiram-like reaction has occurred when metronidazole was used with IV sulfamethoxazole; trimethoprim, SMX-TMP. This reaction would not be expected to occur with oral sulfamethoxazole; trimethoprim, SMX-TMP.
    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: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole; therefore, it should be used cautiously when adminstered with sulfamethoxazole; trimethoprim, which has a possible risk for QT prolongation and TdP. Also, medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Intravenous sulfamethoxazole; trimethoprim, SMX-TMP contains ethanol. A disulfiram-like reaction has occurred when metronidazole was used with IV sulfamethoxazole; trimethoprim, SMX-TMP. This reaction would not be expected to occur with oral sulfamethoxazole; trimethoprim, SMX-TMP. (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.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering sulfamethoxazole with boceprevir due to an increased potential for sulfamethoxazole-related adverse events. If sulfamethoxazole dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of sulfamethoxazole. Sulfamethoxazole is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated sulfamethoxazole plasma concentrations.
    Bosentan: (Moderate) Sulfamethoxazole potently inhibits CYP2C9 and may theoretically lead to elevated plasma concentrations of bosentan when coadministered. Monitor for potential adverse effects of bosentan during coadministration. Excessive bosentan dosage may result in hypotension or elevated hepatic enzymes.
    Bromocriptine: (Moderate) 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.
    Budesonide; Formoterol: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Buprenorphine: (Major) Buprenorphine should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim, SMX-TMP, Cotrimoxazole. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim, SMX-TMP, Cotrimoxazole. Buprenorphine has also been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
    Buprenorphine; Naloxone: (Major) Buprenorphine should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim, SMX-TMP, Cotrimoxazole. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim, SMX-TMP, Cotrimoxazole. Buprenorphine has also been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval.
    Canagliflozin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Canagliflozin; Metformin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Candesartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Candesartan; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Capecitabine: (Moderate) Use caution if coadministration of capecitabine with sulfamethoxazole is necessary, and monitor for an increase in sulfamethoxazole-related adverse reactions. Sulfamethoxazole is a CYP2C9 substrate; capecitabine and/or its metabolites are thought to be inhibitors of CYP2C9. In a drug interaction study, the mean AUC of another CYP2C9 substrate, S-warfarin (single dose), significantly increased after coadministration with capecitabine; the maximum observed INR value also increased by 91%.
    Captopril: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Captopril; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Carbamazepine: (Moderate) The risk for developing leukopenia and/or thrombocytopenia can be increased if other bone marrow depressants are used with sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Megaloblastic anemia can occur when sulfamethoxazole; trimethoprim, SMX-TMP is used in patients who are taking other folate antagonists. These agents include carbamazepine. If these agents are used concomitantly, close observation of blood counts is warranted.
    Ceritinib: (Major) Avoid coadministration of ceritinib with sulfamethoxazole due to increased sulfamethoxazole exposure; additive QT prolongation may also occur. If coadministration is unavoidable, monitor for sulfamethoxazole-related adverse reactions. Periodically monitor electrolytes and ECGs; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib is a CYP2C9 inhibitor that causes concentration-dependent prolongation of the QT interval. Sulfamethoxazole is primarily metabolized by CYP2C9; QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) has been reported during postmarketing use of sulfamethoxazole; trimethoprim.
    Chloramphenicol: (Major) The risk for developing leukopenia and/or thrombocytopenia can be increased if other bone marrow depressants are used with sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Megaloblastic anemia can occur when sulfamethoxazole; trimethoprim, SMX-TMP is used in patients who are taking other folate antagonists. These agents include chloramphenicol. If these agents are used concomitantly, close observation of blood counts is warranted.
    Chloroprocaine: (Major) Ester-type local anesthetics are metabolized to PABA. Para-aminobenzoic acid, PABA, in turn, antagonizes the effects of sulfonamides. Thus, ester-type local anesthetics should not be used in patients receiving sulfonamides.
    Chloroquine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include chloroquine.
    Chlorothiazide: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Chlorpromazine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include chlorpromazine.
    Chlorpropamide: (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. Also, taking these drugs together may increase risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas
    Chlorthalidone: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Chlorthalidone; Clonidine: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    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.
    Chondroitin; Glucosamine: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Ciprofloxacin: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include ciprofloxacin.
    Cisapride: (Severe) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. QT prolongation resulting in ventricular tachycardia and TdP have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Because of the potential for TdP, concurrent use is contraindicated.
    Citalopram: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include citalopram.
    Citric Acid; Potassium Citrate: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Citric Acid; Potassium Citrate; Sodium Citrate: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Clarithromycin: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include clarithromycin.
    Clomipramine: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include tricyclic antidepressants.
    Clopidogrel: (Moderate) At high concentrations in vitro, clopidogrel inhibits the activity of CYP2C9. Thus, clopidogrel could increase plasma concentrations of drugs metabolized by this isoenzyme, such as sulfamethoxazole. Although there are no in vivo data with which to predict the magnitude or clinical significance of this potential interaction, caution should be used when sulfamethoxazole is coadministered with clopidogrel.
    Clozapine: (Major) The risk for developing leukopenia and/or thrombocytopenia can be increased if other bone marrow depressants are used with trimethoprim-sulfamethoxazole, SMX-TMP, cotrimoxazole. Megaloblastic anemia can occur when sulfamethoxazole; trimethoprim, SMX-TMP is used in patients who are taking other folate antagonists. These agents include: clozapine. If these agents are used concomitantly, close observation of blood counts is warranted. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include clozapine.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when elvitegravir is administered with sulfamethoxazole; trimethoprim, SMX-TMP as there is a potential for decreased sulfamethoxazole concentrations. Sulfamethoxazole is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when elvitegravir is administered with sulfamethoxazole; trimethoprim, SMX-TMP as there is a potential for decreased sulfamethoxazole concentrations. Sulfamethoxazole is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
    Codeine; Phenylephrine; Promethazine: (Moderate) Promethazine carries a possible risk of QT prolongation. Sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole is associated with a possible risk for QT prolongation and TdP and should be used cautiously with promethazine.
    Codeine; Promethazine: (Moderate) Promethazine carries a possible risk of QT prolongation. Sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole is associated with a possible risk for QT prolongation and TdP and should be used cautiously with promethazine.
    Crizotinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with sulfamethoxazole; trimethoprim. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) has also been reported during postmarketing use of sulfamethoxazole; trimethoprim. (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with sulfamethoxazole; trimethoprim. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) has also been reported during postmarketing use of sulfamethoxazole; trimethoprim.
    Cyclobenzaprine: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include cyclobenzaprine.
    Cyclosporine: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and cyclosporine. There have been reports of significant, but reversible nephrotoxicity with coadministration in renal transplant patients. In addition, there are case reports of reduced exposure to cyclosporine in patients receiving concomitant sulfonamides. Monitor renal function and cyclosporine concentrations if concomitant use is required.
    Dapagliflozin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Dapagliflozin; Metformin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Dapagliflozin; Saxagliptin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Dapsone: (Major) Agranulocytosis has been reported in the second to third month of weekly concomitant treatment with dapsone and other hemolytic agents such as folic acid antagonists (e.g., trimethoprim, sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole). These combinations increase the likelihood of adverse hematologic events. Concurrent administration of dapsone with trimethoprim increases the plasma concentrations of both drugs. The efficacy of dapsone is increased, which may provide a therapeutic advantage in the treatment of Pneumocystis pneumonia; however, an increase in the frequency and severity of dapsone toxicity (methemoglobinemia, hemolytic anemia) also has been noted.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Ritonavir can increase the AUC of trimethoprim by 20%. Conversely, ritonavir can decrease the AUC of sulfamethoxazole by 20%. However, the Cmax of trimethoprim and sulfamethoxazole was not affected. In addition, both ritonavir and sulfamethoxazole; trimethoprim are associated with QT prolongation; concomitant use increases the risk of QT prolongation. (Minor) According to the manufacturer, no dosage adjustments are required when trimethoprim is administered with dasabuvir; ombitasvir; paritaprevir; ritonavir; however, use of these drugs together may result in elevated dasabuvir plasma concentrations. Trimethoprim inhibits CYP2C8, an enzyme primarily responsible for the metabolism of dasabuvir. Caution and close monitoring are advised if these drugs are administered together. (Minor) Ritonavir can increase the AUC of trimethoprim by 20%. Conversely, ritonavir can decrease the AUC of sulfamethoxazole by 20%. However, the Cmax of trimethoprim and sulfamethoxazole was not affected.
    Dasatinib: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include dasatinib.
    Degarelix: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include degarelix.
    Desflurane: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include halogenated anesthetics.
    Desipramine: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include tricyclic antidepressants.
    Deutetrabenazine: (Moderate) For patients taking a deutetrabenazine dosage more than 24 mg/day with sulfamethoxazole; trimethoprim, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) has been reported during postmarketing use of sulfamethoxazole; trimethoprim.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Dextromethorphan; Promethazine: (Moderate) Promethazine carries a possible risk of QT prolongation. Sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole is associated with a possible risk for QT prolongation and TdP and should be used cautiously with promethazine.
    Dextromethorphan; Quinidine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include quinidine.
    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.
    Digoxin: (Major) Because both trimethoprim and digoxin undergo tubular secretion, trimethoprim can interfere with the renal tubular secretion of digoxin when administered concomitantly. The renal clearance of digoxin decreased significantly in elderly subjects receiving trimethoprim for 14 days, resulting in a 22% increase in digoxin concentrations. Similar changes were not noted in a single-dose study of young healthy volunteers. Patients receiving digoxin, especially the elderly, should be monitored carefully for digoxin toxicity if trimethoprim is added.
    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.
    Disopyramide: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include disopyramide.
    Disulfiram: (Major) The ingestion of ethanol by patients receiving disulfiram causes an extremely unpleasant reaction that can last from 30 minutes to several hours. Intravenous sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole contains ethanol and should not be co-administered with disulfiram. This reaction would not be expected to occur with oral sulfamethoxazole; trimethoprim.
    Dofetilide: (Severe) Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). QT prolongation resulting in ventricular tachycardia and TdP have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Because of the potential for TdP, concurrent use is contraindicated. (Severe) The concurrent use of dofetilide with trimethoprim alone or in combination with sulfamethoxazole is contraindicated. Trimethoprim is an inhibitor of renal cationic secretion and decreases the renal tubular secretion of dofetilide. The combination of trimethoprim 160 mg and 800 mg sulfamethoxazole co-administered twice daily with dofetilide (500 mcg BID) for 4 days has been shown to increase dofetilide AUC by 93% and Cmax by 103%.
    Dolasetron: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include dolasetron.
    Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole.
    Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. (Moderate) Cationic drugs that are eliminated by renal tubular secretion, such as trimethoprim, may decrease memantine elimination by competing for common renal tubular transport systems. Although this interaction is theoretical, careful patient monitoring and dose adjustment of memantine and/or trimethoprim is recommended.
    Doxepin: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include tricyclic antidepressants.
    Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as sulfamethoxazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Dronabinol, THC: (Major) Use caution if coadministration of dronabinol with sulfamethoxazole is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; sulfamethoxazole is a moderate inhibitor of CYP2C9. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Dronedarone: (Severe) The concomitant use of dronedarone with other drugs that prolong the QTc and that may induce torsade de pointes (TdP) is contraindicated. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Additionally, dronedarone is metabolized by and is an inhibitor of CYP3A. Sulfamethoxazole is a substrate for CYP3A4. The concomitant administration of dronedarone and sulfamethoxazole may result in increased exposure of sulfamethoxazole.
    Droperidol: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include droperidol.
    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. (Minor) L-methylfolate and trimethoprim should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with trimethoprim. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Dulaglutide: (Moderate) Sulfonamides may enhance the hypoglycemic action of incretin mimetics and other antidiabetic agents. 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. Patients should be closely monitored for this potential pharmacodynamic interaction while receiving any of these drugs in combination with incretin mimetics.
    Efavirenz: (Major) Coadministration of efavirenz and sulfamethoxazole; trimethoprim may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. QT prolongation resulting in ventricular tachycardia and TdP has been reported during post-marketing use of sulfamethoxazole; trimethoprim.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Coadministration of efavirenz and sulfamethoxazole; trimethoprim may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Although data are limited, the manufacturer of efavirenz recommends an alternative antiretroviral be considered for patients receiving medications with a known risk for TdP. QT prolongation resulting in ventricular tachycardia and TdP has been reported during post-marketing use of sulfamethoxazole; trimethoprim.
    Eliglustat: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include sulfamethoxazole; trimethoprim, SMX-TMP.
    Eltrombopag: (Moderate) Eltrombopag is metabolized by CYP2C8. The significance of administering inhibitors of CYP2C8, such as trimethoprim, on the systemic exposure of eltrombopag has not been established. Monitor patients for signs of eltrombopag toxicity if these drugs are coadministered.
    Elvitegravir: (Moderate) Caution is warranted when elvitegravir is administered with sulfamethoxazole; trimethoprim, SMX-TMP as there is a potential for decreased sulfamethoxazole concentrations. Sulfamethoxazole is a substrate of CYP2C9, while elvitegravir is a CYP2C9 inducer.
    Empagliflozin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Empagliflozin; Linagliptin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents, such as linagliptin. (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Empagliflozin; Metformin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include rilpivirine.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include rilpivirine.
    Enalapril, Enalaprilat: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Enalapril; Felodipine: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Enalapril; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Enflurane: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include halogenated anesthetics.
    Entecavir: (Moderate) Both entecavir and trimethoprim are secreted by active tubular secretion. In theory, coadministration of entecavir with trimethoprim may increase the serum concentrations of either drug due to competition for the drug elimination pathway.
    Enzalutamide: (Moderate) Monitor for decreased efficacy of sulfamethoxazole if coadministration with enzalutamide is necessary. Sulfamethoxazole is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Concomitant use may decrease sulfamethoxazole plasma concentrations.
    Eplerenone: (Major) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Trimethoprim should be used with caution with other drugs known to cause significant hyperkalemia such as eplerenone.
    Eprosartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Eribulin: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include eribulin.
    Erythromycin: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include erythromycin.
    Erythromycin; Sulfisoxazole: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include erythromycin.
    Escitalopram: (Moderate) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as sulfamethoxazole; trimethoprim, should be done with caution and close monitoring.
    Esomeprazole; 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.
    Ester local anesthetics: (Major) Ester-type local anesthetics are metabolized to PABA. Para-aminobenzoic acid, PABA, in turn, antagonizes the effects of sulfonamides. Thus, ester-type local anesthetics should not be used in patients receiving sulfonamides.
    Estradiol Cypionate; Medroxyprogesterone: (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: (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: (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; Desogestrel: (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; Ethynodiol Diacetate: (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; Etonogestrel: (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; 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.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; 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. (Minor) Folate antagonists, such as trimethoprim, especially when used in high doses or over a prolonged period, inhibit dihydrofolate reductase and thus may inhibit the action of folic acid, vitamin B9. (Minor) L-methylfolate and trimethoprim should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with trimethoprim. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    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; Norethindrone Acetate; 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.
    Ethinyl 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.
    Ethinyl Estradiol; Norethindrone; 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.
    Ethinyl 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; 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.
    Exenatide: (Moderate) Sulfonamides may enhance the hypoglycemic action of incretin mimetics and other antidiabetic agents. 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. Patients should be closely monitored for this potential pharmacodynamic interaction while receiving any of these drugs in combination with incretin mimetics.
    Ezogabine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include ezogabine.
    Fenofibric Acid: (Minor) At therapeutic concentrations, fenofibric acid is a mild-to-moderate inhibitor of CYP2C9. Concomitant use of fenofibric acid with CYP2C9 substrates, such as sulfamethoxazole, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C9 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of sulfamethoxazole during coadministration with fenofibric acid.
    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.
    Fingolimod: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include fingolimod.
    Flecainide: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include flecainide.
    Fluconazole: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include fluconazole.
    Fluorouracil, 5-FU: (Major) Use of other folate antagonists should be avoided during therapy with sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Hematologic toxicity, such as leukopenia and/or thrombocytopenia, can be increased by concurrent use of fluorouracil, 5-FU or other bone marrow depressants. (Major) Use of other folate antagonists should be avoided during therapy with trimethoprim. Hematologic toxicity can be increased by concurrent use of fluorouracil, 5-FU.
    Fluoxetine; Olanzapine: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include olanzapine.
    Fluphenazine: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation that should be used cautiously with sulfamethoxazole; trimethoprim include fluphenazine.
    Fluticasone; Salmeterol: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Fluticasone; Vilanterol: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    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.
    Fluvoxamine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and sulfamethoxazole; trimethoprim. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim.
    Folic Acid, Vitamin B9: (Minor) Folate antagonists, such as trimethoprim, especially when used in high doses or over a prolonged period, inhibit dihydrofolate reductase and thus may inhibit the action of folic acid, vitamin B9. (Minor) L-methylfolate and trimethoprim should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with trimethoprim. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Food: (Moderate) The incidence of marijuana associated adverse effects may change following coadministration with sulfamethoxazole. Sulfamethoxazole is an inhibitor of CYP2C9, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (Delta-9-THC). When given concurrently with sulfamethoxazole, the amount of Delta-9-THC converted to the active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) may be reduced. These changes in Delta-9-THC and 11-OH-THC plasma concentrations may result in an altered marijuana adverse event profile.
    Formoterol: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Formoterol; Mometasone: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as sulfamethoxazole . Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). QT prolongation resulting in ventricular tachycardia and TdP has also been reported during postmarketing use of sulfamethoxazole; trimethoprim. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment. (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as trimethoprim. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). QT prolongation resulting in ventricular tachycardia and TdP has also been reported during postmarketing use of sulfamethoxazole; trimethoprim. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Fosinopril: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Fosphenytoin: (Moderate) Concomitant use of sulfamethoxazole with fosphenytoin (which is metabolized to phenytoin) may result in increased serum concentrations of phenytoin and increase the risk for adverse reactions. Phenytoin is a substrate of hepatic isoenzyme CYP2C9; sulfamethoxazole is an inhibitor of this enzyme. Caution and close monitoring of phenytoin serum concentrations are advised if these drugs are used together; dosage adjustments may be necessary in some patients. Monitor for signs of phenytoin toxicity. (Moderate) The half-life of phenytoin may be increased when trimethoprim is given concurrently with phenytoin. It is thought that trimethoprim may interfere with phenytoin hepatic metabolism. Reduced phenytoin clearance can lead to toxicity. Phenytoin or fosphenytoin doses may need to be reduced during concomitant use of trimethoprim.
    Ganciclovir: (Moderate) Use ganciclovir and sulfamethoxazole; trimethoprim together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
    Gemifloxacin: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include gemifloxacin.
    Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and sulfamethoxazole together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim. (Moderate) Use gemtuzumab ozogamicin and trimethoprim together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim.
    Glimepiride: (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. Also, taking these drugs together may increase risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas
    Glimepiride; Pioglitazone: (Moderate) It is possible that an increase in the exposure of pioglitazone may occur when coadministered with other drugs that inhibit CYP2C8 such as trimethoprim. Monitor for changes in glycemic control if trimethoprim is coadministered with pioglitazone. (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. Also, taking these drugs together may increase risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas
    Glimepiride; Rosiglitazone: (Moderate) It is possible that an increase in the exposure of rosiglitazone may occur when coadministered with drugs that inhibit CYP2C8 such as trimethoprim. Patients should be monitored for changes in glycemic control if any CYP2C8 inhibitors are coadministered with rosiglitazone. (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. Also, taking these drugs together may increase risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas
    Glipizide: (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. Also, taking these drugs together may increase risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas
    Glipizide; Metformin: (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. Also, taking these drugs together may increase risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas
    Glucosamine: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Glyburide: (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. Also, taking these drugs together may increase risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas
    Glyburide; Metformin: (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. Also, taking these drugs together may increase risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas
    Glycopyrrolate; Formoterol: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Goserelin: (Moderate) Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with goserelin include sulfamethoxazole; trimethoprim, SMX-TMP.
    Granisetron: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include granisetron.
    Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Halogenated Anesthetics: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include halogenated anesthetics.
    Haloperidol: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include haloperidol.
    Halothane: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include halogenated anesthetics.
    Hetastarch; Dextrose; Electrolytes: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Hydrochlorothiazide, HCTZ: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Hydrochlorothiazide, HCTZ; Losartan: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors. (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.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Hydrochlorothiazide, HCTZ; Moexipril: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Hydrochlorothiazide, HCTZ; Propranolol: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Hydrochlorothiazide, HCTZ; Quinapril: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Major) Trimethoprim has a potassium-sparing effect and may induce hyperkalemia, especially in patients with pre-existing risk factors for hyperkalemia (e.g., renal disease). Patients, especially those with renal dysfunction, should be carefully monitored for hyperkalemia during concomitant use of potassium-sparing diuretics and trimethoprim.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Hydrochlorothiazide, HCTZ; Triamterene: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Major) Trimethoprim has a potassium-sparing effect and may induce hyperkalemia, especially in patients with pre-existing risk factors for hyperkalemia (e.g., renal disease). Patients, especially those with renal dysfunction, should be carefully monitored for hyperkalemia during concomitant use of potassium-sparing diuretics and trimethoprim. (Major) Use of other folate antagonists should be avoided during therapy with sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Hematologic toxicity, such as leukopenia and/or thrombocytopenia, can be increased by concurrent use of triamterene or other bone marrow depressants.
    Hydrochlorothiazide, HCTZ; Valsartan: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration. (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and sulfamethoxazole; trimethoprim. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes (TdP) have been reported with the use of hydroxychloroquine. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim.
    Hydroxyzine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include sulfamethoxazole; trimethoprim, SMX-TMP, Cotrimoxazole.
    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.
    Ibritumomab Tiuxetan: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts. (Moderate) Use potassium phosphate cautiously with trimethoprim (especially high dose), as both drugs increase serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Patients should have serum potassium concentration determinations at periodic intervals.
    Ibutilide: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include ibutilide.
    Iloperidone: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include iloperidone.
    Imipramine: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include tricyclic antidepressants.
    Incretin Mimetics: (Moderate) Sulfonamides may enhance the hypoglycemic action of incretin mimetics and other antidiabetic agents. 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. Patients should be closely monitored for this potential pharmacodynamic interaction while receiving any of these drugs in combination with incretin mimetics.
    Indacaterol: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Indacaterol; Glycopyrrolate: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Indinavir: (Minor) Concomitant administration of indinavir and trimethoprim should be done with caution. Administration of indinavir and sulfamethoxazole; trimethoprim, SMX-TMP significantly increased the AUC of trimethoprim. There was no effect on the AUC of indinavir or sulfamethoxazole.
    Indomethacin: (Major) Avoid the concomitant use of sulfamethoxazole and indomethacin as coadministration may result in increased serum concentrations of sulfamethoxazole. Coadministration may increase the risk of sulfamethoxazole toxicity.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with sulfamethoxazole due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim. (Major) Avoid coadministration of inotuzumab ozogamicin with trimethoprim due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim.
    Insulin Degludec; Liraglutide: (Moderate) Sulfonamides may enhance the hypoglycemic action of incretin mimetics and other antidiabetic agents. 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. Patients should be closely monitored for this potential pharmacodynamic interaction while receiving any of these drugs in combination with incretin mimetics.
    Insulin Glargine; Lixisenatide: (Moderate) Sulfonamides may enhance the hypoglycemic action of incretin mimetics and other antidiabetic agents. 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. Patients should be closely monitored for this potential pharmacodynamic interaction while receiving any of these drugs in combination with incretin mimetics.
    Insulins: (Moderate) Monitor patients receiving sulfonamides concomitantly with insulin for changes in glycemic control. Sulfonamides may enhance the hypoglycemic action of insulin. 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.
    Iodine; Potassium Iodide, KI: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Irbesartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Iron Salts: (Minor) Folate antagonists, such as trimethoprim, especially when used in high doses or over a prolonged period, inhibit dihydrofolate reductase and thus may inhibit the action of folic acid, vitamin B9.
    Isoflurane: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include halogenated anesthetics.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15 to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. The drugs are often given clinically together with certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy. (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15% to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. Additionally, sulfamethoxazole; trimethoprim may increase the serum concentration of rifampin. The drugs are often given together for certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy and increased rifampin toxicity
    Isoniazid, INH; Rifampin: (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15 to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. The drugs are often given clinically together with certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy. (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15% to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. Additionally, sulfamethoxazole; trimethoprim may increase the serum concentration of rifampin. The drugs are often given together for certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy and increased rifampin toxicity
    Itraconazole: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include sulfamethoxazole; trimethoprim, SMX-TMP.
    Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sulfamethoxazole; trimethoprim, SMX-TMP. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
    Ketoconazole: (Major) Ketoconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ketoconazole include sulfamethoxazole; trimethoprim, SMX-TMP.
    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. (Moderate) Concomitant use of trimethoprim and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
    Lamotrigine: (Moderate) Lamotrigine inhibits dihydrofolate reductase. Caution should be exercised when administering trimethoprim, which also inhibits this enzyme.
    Lansoprazole; 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.
    Lapatinib: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include lapatinib.
    Lenvatinib: (Major) Sulfamethoxazole; trimethoprim, SMX-TMP, Cotrimoxazole should be used cautiously and with close monitoring with lenvatinib. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim.
    Lesinurad: (Moderate) Use lesinurad and sulfamethoxazole together with caution; sulfamethoxazole may increase the systemic exposure of lesinurad. Sulfamethoxazole is an inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
    Lesinurad; Allopurinol: (Moderate) Use lesinurad and sulfamethoxazole together with caution; sulfamethoxazole may increase the systemic exposure of lesinurad. Sulfamethoxazole is an inhibitor of CYP2C9, and lesinurad is a CYP2C9 substrate.
    Leucovorin: (Minor) Racemic leucovorin may be used to offset the toxicity of folate antagonists such as trimethoprim; however, the concomitant use of leucovorin with sulfamethoxazole; trimethoprim for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection was associated with an increased risk of treatment failure and morbidity. Levoleucovorin may result in the same effect. (Minor) The concomitant use of leucovorin with sulfamethoxazole; trimethoprim, for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection was associated with an increased risk of treatment failure and morbidity. Levoleucovorin may result in the same effect.
    Leuprolide: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include sulfamethoxazole; trimethoprim. (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include trimethoprim.
    Leuprolide; Norethindrone: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include sulfamethoxazole; trimethoprim. (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include trimethoprim. (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.
    Levalbuterol: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Levofloxacin: (Major) Use sulfamethoxazole; trimethoprim and levofloxacin together with caution due to an increased risk for QT prolongation and torsade de pointes (TdP). Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Rare cases of TdP have been reported during postmarketing surveillance in patients receiving levofloxacin. QT prolongation, resulting in ventricular tachycardia and TdP, has been reported during postmarketing use of sulfamethoxazole; trimethoprim.
    Levoleucovorin: (Minor) Racemic leucovorin may be used to offset the toxicity of folate antagonists such as trimethoprim; however, the concomitant use of leucovorin with sulfamethoxazole; trimethoprim for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection was associated with an increased risk of treatment failure and morbidity. Levoleucovorin may result in the same effect. (Minor) The concomitant use of leucovorin with sulfamethoxazole; trimethoprim, for the acute treatment of Pneumocystis carinii pneumonia in patients with HIV infection was associated with an increased risk of treatment failure and morbidity. Levoleucovorin may result in the same effect.
    Levomefolate: (Minor) L-methylfolate and trimethoprim should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with trimethoprim. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    Levomefolate; Mecobalamin; Pyridoxal-5-phosphate: (Minor) L-methylfolate and trimethoprim should be used together cautiously. Plasma concentrations of L-methylfolate may be reduced when used concomitantly with trimethoprim. Monitor patients for decreased efficacy of L-methylfolate if these agents are used together.
    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.
    Linagliptin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents, such as linagliptin.
    Linagliptin; Metformin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents, such as linagliptin. (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Liraglutide: (Moderate) Sulfonamides may enhance the hypoglycemic action of incretin mimetics and other antidiabetic agents. 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. Patients should be closely monitored for this potential pharmacodynamic interaction while receiving any of these drugs in combination with incretin mimetics.
    Lisinopril: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Lithium: (Moderate) Sulfamethoxazole; trimethoprim should be used cautiously and with close monitoring with lithium. Lithium has been associated with QT prolongation. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim.
    Lixisenatide: (Moderate) Sulfonamides may enhance the hypoglycemic action of incretin mimetics and other antidiabetic agents. 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. Patients should be closely monitored for this potential pharmacodynamic interaction while receiving any of these drugs in combination with incretin mimetics.
    Long-acting beta-agonists: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Loperamide: (Moderate) If these drugs are used together, the plasma concentrations of loperamide may increase. Loperamide is a substrate for CYP2C8. Trimethoprim has been shown in vitro and in studies of healthy human volunteers to selectively inhibit the CYP2C8 isoenzyme. Monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects. (Moderate) Loperamide should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). Monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Loperamide; Simethicone: (Moderate) If these drugs are used together, the plasma concentrations of loperamide may increase. Loperamide is a substrate for CYP2C8. Trimethoprim has been shown in vitro and in studies of healthy human volunteers to selectively inhibit the CYP2C8 isoenzyme. Monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects. (Moderate) Loperamide should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Coadministration may increase the risk for QT prolongation and torsade de pointes (TdP). Monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Lopinavir; Ritonavir: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include lopinavir; ritonavir. In addition, ritonavir can increase the AUC of trimethoprim by 20%. Conversely, ritonavir can decrease the AUC of sulfamethoxazole by 20%. However, the Cmax of trimethoprim and sulfamethoxazole was not affected (Major) Ritonavir can increase the AUC of trimethoprim by 20%. Conversely, ritonavir can decrease the AUC of sulfamethoxazole by 20%. However, the Cmax of trimethoprim and sulfamethoxazole was not affected. In addition, both ritonavir and sulfamethoxazole; trimethoprim are associated with QT prolongation; concomitant use increases the risk of QT prolongation. (Minor) Ritonavir can increase the AUC of trimethoprim by 20%. Conversely, ritonavir can decrease the AUC of sulfamethoxazole by 20%. However, the Cmax of trimethoprim and sulfamethoxazole was not affected.
    Losartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors. (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.
    Lumacaftor; Ivacaftor: (Minor) Concomitant use of sulfamethoxazole; trimethoprim and lumacaftor; ivacaftor may alter sulfamethoxazole; trimethoprim, SMX-TMP, Cotrimoxazole exposure. Sulfamethoxazole is a substrate of CYP2C9; in vitro data suggest it is also a substrate for the P-glycoprotein (P-gp) drug transporter. In vitro data suggest that lumacaftor; ivacaftor may induce and/or inhibit CYP2C9 and P-gp. The net effect of lumacaftor; ivacaftor on CYP2C9-mediated metabolism and P-gp transport is not clear, but substrate exposure may be affected leading to decreased efficacy or increased or prolonged therapeutic effects and adverse events.
    Lumacaftor; Ivacaftor: (Minor) Increased monitoring is recommended if ivacaftor is administered concurrently with CYP2C9 substrates, such as sulfamethoxazole; trimethoprim, SMX-TMP. In vitro studies showed ivacaftor to be a weak inhibitor of CYP2C9. Co-administration may lead to increased exposure to CYP2C9 substrates; however, the clinical impact of this has not yet been determined.
    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.
    Maprotiline: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include maprotiline.
    Mefenamic Acid: (Moderate) Mefenamic acid is a substrate for CYP450 2C9. Inhibitors of the 2C9 isoenzyme, such as trimethoprim, may lead to increased serum concentrations of mefenamic acid. If administered concurrently with mefenamic acid, monitor for NSAID related side effects.
    Mefloquine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include mefloquine.
    Meglitinides: (Moderate) Sulfonamides may induce hypoglycemia by increasing the secretion of insulin from the pancreas. Therefore, a pharmacodynamic interaction leading to an increased risk of hypoglycemia may occur in patients taking antidiabetic agents and sulfonamides.
    Memantine: (Moderate) Cationic drugs that are eliminated by renal tubular secretion, such as trimethoprim, may decrease memantine elimination by competing for common renal tubular transport systems. Although this interaction is theoretical, careful patient monitoring and dose adjustment of memantine and/or trimethoprim is recommended.
    Meperidine; Promethazine: (Moderate) Promethazine carries a possible risk of QT prolongation. Sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole is associated with a possible risk for QT prolongation and TdP and should be used cautiously with promethazine.
    Mercaptopurine, 6-MP: (Minor) Enhanced bone marrow suppression has been noted in some patients receiving sulfamethoxazole; trimethoprim, SMX-TMP concurrently with mercaptopurine.
    Mestranol; 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.
    Metaproterenol: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Metformin: (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Metformin; Pioglitazone: (Moderate) It is possible that an increase in the exposure of pioglitazone may occur when coadministered with other drugs that inhibit CYP2C8 such as trimethoprim. Monitor for changes in glycemic control if trimethoprim is coadministered with pioglitazone. (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Metformin; Repaglinide: (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. (Minor) The coadministration of trimethoprim and repaglinide was found to increase the plasma concentration of repaglinide. This interaction is most likely due to trimethoprim's inhibition of the CYP2C8 isoenzyme. The possibility of an increased risk of hypoglycemia should be considered during concomitant use of trimethoprim and repaglinide.
    Metformin; Rosiglitazone: (Moderate) It is possible that an increase in the exposure of rosiglitazone may occur when coadministered with drugs that inhibit CYP2C8 such as trimethoprim. Patients should be monitored for changes in glycemic control if any CYP2C8 inhibitors are coadministered with rosiglitazone. (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Metformin; Saxagliptin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Metformin; Sitagliptin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Methadone: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include methadone.
    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: (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.
    Methotrexate: (Major) Methotrexate is partially bound to plasma proteins, and drugs that can displace methotrexate from these proteins, such as sulfonamides could cause methotrexate-induced toxicity. Due to the potential toxicity of methotrexate, interactions with sulfonamides can be very serious even if methotrexate is administered in low doses. (Moderate) Use of other folate antagonists, such as methotrexate, should be avoided during therapy with trimethoprim. Hematologic toxicity can be increased by concurrent use of methotrexate.
    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.
    Methyclothiazide: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Metolazone: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Metronidazole: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole; therefore, it should be used cautiously when adminstered with sulfamethoxazole; trimethoprim, which has a possible risk for QT prolongation and TdP. Also, medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Intravenous sulfamethoxazole; trimethoprim, SMX-TMP contains ethanol. A disulfiram-like reaction has occurred when metronidazole was used with IV sulfamethoxazole; trimethoprim, SMX-TMP. This reaction would not be expected to occur with oral sulfamethoxazole; trimethoprim, SMX-TMP.
    Midostaurin: (Major) The concomitant use of midostaurin and sulfamethoxazole; trimethoprim may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. QT prolongation resulting in ventricular tachycardia and torsade de pointes has been reported during postmarketing use of sulfamethoxazole; trimethoprim.
    Mifepristone, RU-486: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include mifepristone, RU-486.
    Miglitol: (Moderate) Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Therefore, a pharmacodynamic interaction leading to an increased risk of hypoglycemia may occur in patients taking antidiabetic agents and sulfonamides.
    Mirtazapine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and sulfamethoxazole; trimethoprim. Coadminister with caution. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) has been reported during postmarketing use of sulfamethoxazole; trimethoprim. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Moexipril: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Moxifloxacin: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include moxifloxacin.
    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; 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.
    Naproxen; Sumatriptan: (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.
    Nebivolol; Valsartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Nilotinib: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include nilotinib.
    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.
    Norfloxacin: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include norfloxacin.
    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.
    Nortriptyline: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include tricyclic antidepressants.
    Octreotide: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include octreotide.
    Ofloxacin: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include ofloxacin.
    Olanzapine: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include olanzapine.
    Olmesartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Olodaterol: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Ritonavir can increase the AUC of trimethoprim by 20%. Conversely, ritonavir can decrease the AUC of sulfamethoxazole by 20%. However, the Cmax of trimethoprim and sulfamethoxazole was not affected. In addition, both ritonavir and sulfamethoxazole; trimethoprim are associated with QT prolongation; concomitant use increases the risk of QT prolongation. (Minor) Ritonavir can increase the AUC of trimethoprim by 20%. Conversely, ritonavir can decrease the AUC of sulfamethoxazole by 20%. However, the Cmax of trimethoprim and sulfamethoxazole was not affected.
    Ondansetron: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include ondansetron.
    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.
    Oritavancin: (Moderate) Sulfamethoxazole is metabolized by CYP2C9; oritavancin is a weak CYP2C9 inhibitor. Coadministration may result in elevated sulfamethoxazole plasma concentrations. If these drugs are administered concurrently, monitor for sulfamethoxazole toxicity such as diarrhea, anorexia, or nausea.
    Osimertinib: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of sulfamethoxazole with osimertinib is necessary; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) has also been reported during postmarketing use of sulfamethoxazole; trimethoprim. (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of trimethoprim with osimertinib is necessary; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) has also been reported during postmarketing use of sulfamethoxazole; trimethoprim.
    Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of sulfamethoxazole with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. There have been reports of QT prolongation and ventricular arrhythmias including fatal torsade de pointes in postmarketing experience with both oxaliplatin and sulfamethoxazole; trimethoprim. (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of trimethoprim with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. There have been reports of QT prolongation and ventricular arrhythmias including fatal torsade de pointes in postmarketing experience with both oxaliplatin and sulfamethoxazole; trimethoprim.
    Paclitaxel: (Minor) Paclitaxel is a substrate of CYP2C8; in vitro, trimethoprim is a mild inhibitor of CYP2C8. If coadministration is necessary, use caution and monitor for increased paclitaxel side effects, including myelosuppression and peripheral neuropathy. This interaction may also be applicable to combination products containing trimethoprim, including sulfamethoxazole; trimethoprim (also known as SMX-TMP or cotrimoxazole).
    Paliperidone: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include paliperidone.
    Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include sulfamethoxazole; trimethoprim, SMX-TMP, Cotrimoxazole.
    Pasireotide: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include pasireotide.
    Pazopanib: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include pazopanib. Pazopanib is also a weak inhibitor of CYP3A4. Coadministration of pazopanib and sulfamethoxazole; trimethoprim, SMX-TMP, a CYP3A4 substrate, may cause an increase in systemic concentrations of sulfamethoxazole; trimethoprim, SMX-TMP.
    Penicillins: (Minor) Sulfonamides may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. These combinations should be used with caution and patients monitored for increased side effects.
    Pentamidine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include pentamidine.
    Perindopril: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Perindopril; Amlodipine: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Perphenazine: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include perphenazine.
    Perphenazine; Amitriptyline: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include perphenazine. (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include tricyclic antidepressants.
    Phenylephrine; Promethazine: (Moderate) Promethazine carries a possible risk of QT prolongation. Sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole is associated with a possible risk for QT prolongation and TdP and should be used cautiously with promethazine.
    Phenytoin: (Moderate) Concomitant use of sulfamethoxazole with phenytoin may result in increased serum concentrations of phenytoin and increase the risk for adverse reactions. Phenytoin is a substrate of hepatic isoenzyme CYP2C9; sulfamethoxazole is an inhibitor of this enzyme. Caution and close monitoring of phenytoin serum concentrations are advised if these drugs are used together; dosage adjustments may be necessary in some patients. Monitor for signs of phenytoin toxicity. (Moderate) The half-life of phenytoin may be increased with trimethoprim. It is thought that trimethoprim may interfere with phenytoin hepatic metabolism. Reduced phenytoin clearance can lead to toxicity. Phenytoin doses may need to be reduced during concomitant use of trimethoprim.
    Phosphorus Salts: (Moderate) Use potassium phosphate cautiously with trimethoprim (especially high dose), as both drugs increase serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Patients should have serum potassium concentration determinations at periodic intervals.
    Photosensitizing agents: (Moderate) Use photosensitizing agents 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.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as sulfamethoxazole; trimethoprim. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Coadministration may increase the risk for QT prolongation.
    Pimozide: (Severe) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Because of the potential for TdP, concurrent use is contraindicated.
    Pioglitazone: (Moderate) It is possible that an increase in the exposure of pioglitazone may occur when coadministered with other drugs that inhibit CYP2C8 such as trimethoprim. Monitor for changes in glycemic control if trimethoprim is coadministered with pioglitazone.
    Pirbuterol: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Porfimer: (Moderate) Use photosensitizing agents 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.
    Posaconazole: (Major) Posaconazole and sulfamethoxazole should be coadministered with caution due to an increased potential for sulfamethoxazole-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of sulfamethoxazole. These drugs used in combination may result in elevated sulfamethoxazole plasma concentrations, causing an increased risk for sulfamethoxazole-related adverse events.
    Potassium Citrate: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Potassium Iodide, KI: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Potassium Phosphate; Sodium Phosphate: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts. (Moderate) Use potassium phosphate cautiously with trimethoprim (especially high dose), as both drugs increase serum potassium concentrations. Concurrent use can cause hyperkalemia, especially in elderly patients or patients with impaired renal function. Patients should have serum potassium concentration determinations at periodic intervals.
    Potassium Salts: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Potassium: (Moderate) Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia. Trimethoprim should also be used with caution with other drugs known to cause significant hyperkalemia such as potassium salts.
    Potassium-sparing diuretics: (Major) Trimethoprim has a potassium-sparing effect and may induce hyperkalemia, especially in patients with pre-existing risk factors for hyperkalemia (e.g., renal disease). Patients, especially those with renal dysfunction, should be carefully monitored for hyperkalemia during concomitant use of potassium-sparing diuretics and trimethoprim.
    Pralatrexate: (Major) Renal elimination accounts for approximately 34% of the overall clearance of pralatrexate. Concomitant administration of drugs that undergo substantial renal clearance, such as sulfamethoxazole; trimethoprim, SMX-TMP, may result in delayed clearance of pralatrexate.
    Pramlintide: (Moderate) Sulfonamides may induce hypoglycemia by increasing the secretion of insulin from the pancreas. Therefore, a pharmacodynamic interaction leading to an increased risk of hypoglycemia may occur in patients taking antidiabetic agents and sulfonamides.
    Prilocaine: (Minor) Patients treated with prilocaine who are receiving other drugs that can cause methemoglobin formation, such as sulfonamides, are at greater risk for developing methemoglobinemia.
    Prilocaine; Epinephrine: (Minor) Patients treated with prilocaine who are receiving other drugs that can cause methemoglobin formation, such as sulfonamides, are at greater risk for developing methemoglobinemia.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include sulfamethoxazole; trimethoprim, SMX-TMP, Cotrimoxazole.
    Probenecid: (Minor) Probenecid may inhibit the renal transport of sulfonamides. Plasma concentrations of these agents may be increased.
    Procainamide: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include procainamide. (Major) Trimethoprim and procainamide both undergo tubular secretion, and as a result, each drug can interfere with the renal clearance of the other. Although it is not necessary to avoid concomitant use of these two drugs, lower doses of procainamide may be necessary during trimethoprim administration.
    Procaine: (Major) Ester-type local anesthetics are metabolized to PABA. Para-aminobenzoic acid, PABA, in turn, antagonizes the effects of sulfonamides. Thus, ester-type local anesthetics should not be used in patients receiving sulfonamides.
    Prochlorperazine: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include prochlorperazine.
    Promethazine: (Moderate) Promethazine carries a possible risk of QT prolongation. Sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole is associated with a possible risk for QT prolongation and TdP and should be used cautiously with promethazine.
    Propafenone: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include propafenone.
    Protriptyline: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include tricyclic antidepressants.
    Pyrimethamine: (Major) The combination of pyrimethamine with sulfonamides can be synergistic against susceptible organisms, however, bone marrow suppression may be more likely to occur with combination therapy. CBCs should be monitored routinely in patients receiving both drugs simultaneously. Some references suggest routinely administering leucovorin during therapy with pyrimethamine even when used without any of the above drugs. (Major) Use of other folate antagonists should be avoided during therapy with trimethoprim. Hematologic toxicity can be increased by concurrent use of pyrimethamine.
    Pyrimethamine; Sulfadoxine: (Major) The combination of pyrimethamine with sulfonamides can be synergistic against susceptible organisms, however, bone marrow suppression may be more likely to occur with combination therapy. CBCs should be monitored routinely in patients receiving both drugs simultaneously. Some references suggest routinely administering leucovorin during therapy with pyrimethamine even when used without any of the above drugs. (Major) Use of other folate antagonists should be avoided during therapy with trimethoprim. Hematologic toxicity can be increased by concurrent use of pyrimethamine.
    Quetiapine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include quetiapine.
    Quinapril: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Quinidine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include quinidine.
    Ramelteon: (Moderate) Ramelteon should be administered with caution to patients taking CYP2C9 inhibitors, such as sulfamethoxazole. The AUC and Cmax of ramelteon have been elevated > 150% when administered with other CYP2C9 inhibitors. The patient should be monitored closely for toxicity even though ramelteon has a wide therapeutic index.
    Ramipril: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Ranolazine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include ranolazine.
    Regadenoson: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include regadenoson.
    Repaglinide: (Minor) The coadministration of trimethoprim and repaglinide was found to increase the plasma concentration of repaglinide. This interaction is most likely due to trimethoprim's inhibition of the CYP2C8 isoenzyme. The possibility of an increased risk of hypoglycemia should be considered during concomitant use of trimethoprim and repaglinide.
    Ribociclib: (Major) Avoid coadministration of ribociclib with sulfamethoxazole; trimethoprim due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim. Concomitant use may increase the risk for QT prolongation. (Major) Avoid coadministration of ribociclib with sulfamethoxazole; trimethoprim due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) has been reported during postmarketing use of sulfamethoxazole; trimethoprim. Concomitant use may increase the risk for QT prolongation.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with sulfamethoxazole; trimethoprim due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim. Concomitant use may increase the risk for QT prolongation. (Major) Avoid coadministration of ribociclib with sulfamethoxazole; trimethoprim due to an increased risk for QT prolongation and torsade de pointes (TdP). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) has been reported during postmarketing use of sulfamethoxazole; trimethoprim. Concomitant use may increase the risk for QT prolongation.
    Rifabutin: (Moderate) Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15 to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. sulfamethoxazole; trimethoprim, SMX-TMP did not alter the pharmacokinetics of rifabutin.
    Rifampin: (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15 to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. The drugs are often given clinically together with certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy. (Moderate) Rifampin is a potent enzyme inducer. Rifampin can increase the metabolism of sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. A pharmacokinetic effect on the combination has been reported with another rifamycin. Concomitant administration of rifabutin and sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole (double-strength) in 12 HIV-infected patients decreased the AUC of SMX-TMP by about 15% to 20%. Rifabutin decreased the AUC and Cmax of trimethoprim by 14% and 6%, respectively, when rifabutin was given with trimethoprim alone. Additionally, sulfamethoxazole; trimethoprim may increase the serum concentration of rifampin. The drugs are often given together for certain patient populations, so the ultimate clinical significance of a possible pharmacokinetic interaction is not clear. Monitor for therapeutic response to therapy and increased rifampin toxicity
    Rilpivirine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include rilpivirine.
    Risperidone: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include risperidone.
    Ritonavir: (Major) Ritonavir can increase the AUC of trimethoprim by 20%. Conversely, ritonavir can decrease the AUC of sulfamethoxazole by 20%. However, the Cmax of trimethoprim and sulfamethoxazole was not affected. In addition, both ritonavir and sulfamethoxazole; trimethoprim are associated with QT prolongation; concomitant use increases the risk of QT prolongation. (Minor) Ritonavir can increase the AUC of trimethoprim by 20%. Conversely, ritonavir can decrease the AUC of sulfamethoxazole by 20%. However, the Cmax of trimethoprim and sulfamethoxazole was not affected.
    Romidepsin: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include romidepsin.
    Rosiglitazone: (Moderate) It is possible that an increase in the exposure of rosiglitazone may occur when coadministered with drugs that inhibit CYP2C8 such as trimethoprim. Patients should be monitored for changes in glycemic control if any CYP2C8 inhibitors are coadministered with rosiglitazone.
    Sacubitril; Valsartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    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.
    Salmeterol: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    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.
    Saquinavir: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include saquinavir.
    Saxagliptin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Selexipag: (Major) Consider a less frequent dosing regimen (e.g., once daily) when initiating selexipag in patients receiving trimethoprim. Reduce the selexipag dose when trimethoprim is initiated in patients already taking selexipag. Coadministration can be expected to increase exposure to selexipag and its active metabolite. Selexipag is a substrate of CYP2C8; trimethoprim is a moderate CYP2C8 inhibitor.
    Sertraline: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim, SMX-TMP. There have been post-marketing reports of QT prolongation and torsade de pointes (TdP) during treatment with sertraline; therefore, caution is advisable when using sertraline in patients with risk factors for QT prolongation, including concurrent use of other drugs that prolong the QTc interval.
    Sevoflurane: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include halogenated anesthetics.
    Short-acting beta-agonists: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Simvastatin; Sitagliptin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    Sitagliptin: (Moderate) Sulfonamides may enhance the hypoglycemic action of antidiabetic agents. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents.
    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.
    Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with trimethoprim. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a CYP2C8 substrate; trimethoprim is an inhibitor of CYP2C8.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with trimethoprim. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a CYP2C8 substrate; trimethoprim is an inhibitor of CYP2C8.
    Solifenacin: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include solifenacin.
    Sorafenib: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include sorafenib.
    Sotalol: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include sotalol.
    Spironolactone: (Major) Trimethoprim has a potassium-sparing effect and may induce hyperkalemia, especially in patients with pre-existing risk factors for hyperkalemia (e.g., renal disease). Patients, especially those with renal dysfunction, should be carefully monitored for hyperkalemia during concomitant use of potassium-sparing diuretics and trimethoprim.
    Sulfinpyrazone: (Moderate) Sulfamethoxazole is roughly 60 to 70% protein-bound and can potentiate other drugs by displacing them from their binding sites. Drugs that may be affected in this manner include sulfinpyrazone.
    Sulfonylureas: (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. Also, taking these drugs together may increase risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas
    Sunitinib: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include sunitinib.
    Tacrolimus: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include tacrolimus.
    Tamoxifen: (Moderate) Caution is advised with the concomitant use of tamoxifen and sulfamethoxazole; trimethoprim due to an increased risk of QT prolongation and torsade de pointes (TdP). Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim. (Moderate) Caution is advised with the concomitant use of tamoxifen and trimethoprim due to an increased risk of QT prolongation and torsade de pointes (TdP). Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. QT prolongation resulting in ventricular tachycardia and TdP has been reported during postmarketing use of sulfamethoxazole; trimethoprim.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering sulfamethoxazole with telaprevir due to an increased potential for sulfamethoxazole-related adverse events. If sulfamethoxazole dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of sulfamethoxazole. Sulfamethoxazole is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated sulfamethoxazole plasma concentrations.
    Telavancin: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include telavancin.
    Telithromycin: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include telithromycin.
    Telmisartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering sulfamethoxazole. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP2C9; sulfamethoxazole is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered. (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering trimethoprim. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenzymes, with major contributions coming from CYP2C8; trimethoprim is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Terbutaline: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Tetrabenazine: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include tetrabenazine.
    Tetracaine: (Major) Ester-type local anesthetics are metabolized to PABA. Para-aminobenzoic acid, PABA, in turn, antagonizes the effects of sulfonamides. Thus, ester-type local anesthetics should not be used in patients receiving sulfonamides.
    Thiazide diuretics: (Major) Avoid the concomitant use of sulfamethoxazole; trimethoprim and thiazide diuretics. An increased incidence of thrombocytopenia with purpura has been reported in elderly patients during coadministration.
    Thiazolidinediones: (Moderate) Sulfonamides may induce hypoglycemia by increasing the secretion of insulin from the pancreas. Therefore, a pharmacodynamic interaction leading to an increased risk of hypoglycemia may occur in patients taking antidiabetic agents and sulfonamides.
    Thioridazine: (Severe) Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP). QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Because of the potential for TdP, concurrent use is contraindicated.
    Tinidazole: (Severe) IV formulations of sulfamethoxazole; trimethoprim, SMX-TMP contains alcohol and disulfiram-like side effects including nausea, vomiting, headache, flushing, and abdominal cramps may occur if coadministered with tinidazole.
    Tiotropium; Olodaterol: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Tizanidine: (Moderate) Tizanidine should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim. Tizanidine administration may result in QT prolongation. QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Coadministration increases the risk for QT prolongation and torsade de pointes.
    Tolazamide: (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. Also, taking these drugs together may increase risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas
    Tolbutamide: (Moderate) 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. Patients should be closely monitored while receiving any of these drugs in combination with antidiabetic agents. Also, taking these drugs together may increase risk for phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas (Minor) Trimethoprim has been shown to reduce the clearance of unbound tolbutamide and prolong tolbutamide half-life. The reductions in tolbutamide clearance are relatively small. While the risk of enhanced hypoglycemic effects appears low, closely monitor blood glucose during concomitant therapy.
    Tolterodine: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include tolterodine.
    Toremifene: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include toremifene.
    Trandolapril: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Trandolapril; Verapamil: (Major) Avoid the concomitant use of trimethoprim and ACE inhibitors. Concurrent use may result in additive hyperkalemia. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially with pre-existing risk factors for hyperkalemia. Patients, especially those with renal dysfunction, should be monitored for hyperkalemia if concomitant use of ACE inhibitors and trimethoprim is necessary.
    Trazodone: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include trazodone.
    Treprostinil: (Minor) Although pharmacokinetic drug interaction studies have not been conducted, coadministration of treprostinil and trimethoprim, a cytochrome P450 (CYP) 2C8 enzyme inhibitor, may result in increased treprostinil exposure. Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diethanolamine) indicated that coadministration of gemfibrozil, another CYP2C8 inhibitor, results in increased exposure (both Cmax and AUC) to treprostinil. The clinical significance of this interaction with orally inhaled treprostinil and other CYP2C8 inhibitors is unknown.
    Triamterene: (Major) Trimethoprim has a potassium-sparing effect and may induce hyperkalemia, especially in patients with pre-existing risk factors for hyperkalemia (e.g., renal disease). Patients, especially those with renal dysfunction, should be carefully monitored for hyperkalemia during concomitant use of potassium-sparing diuretics and trimethoprim. (Major) Use of other folate antagonists should be avoided during therapy with sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Hematologic toxicity, such as leukopenia and/or thrombocytopenia, can be increased by concurrent use of triamterene or other bone marrow depressants.
    Tricyclic antidepressants: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include tricyclic antidepressants.
    Trifluoperazine: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include trifluoperazine.
    Trimetrexate: (Major) Use of other folate antagonists should be avoided during therapy with sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Hematologic toxicity, such as leukopenia and/or thrombocytopenia, can be increased by concurrent use of trimetrexate or other bone marrow depressants. (Major) Use of other folate antagonists should be avoided during therapy with trimethoprim. Hematologic toxicity can be increased by concurrent use of trimetrexate.
    Trimipramine: (Minor) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include tricyclic antidepressants.
    Triptorelin: (Moderate) Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with triptorelin include sulfamethoxazole. (Moderate) Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with triptorelin include sulfamethoxazole; trimethoprim, SMX-TMP.
    Trospium: (Moderate) Both trospium and trimethoprim are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of trospium or trimethoprim due to competition for the drug elimination pathway. Careful patient monitoring is recommended. For trospium, monitor for anticholinergic effects, such as dry mouth, constipation, blurred vision, urinary retention, or increased CNS effects which are not frequent when the drug is used alone. Trimethoprim dose-related side effects include nausea, vomiting, dizziness, headaches, mental depression/confusion, palpitations, and bone marrow depression. In some patients, a dosage reduction may be required.
    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.
    Umeclidinium; Vilanterol: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include beta-agonists.
    Valganciclovir: (Moderate) Use valganciclovir and sulfamethoxazole; trimethoprim together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
    Valproic Acid, Divalproex Sodium: (Minor) The risk for developing leukopenia and/or thrombocytopenia can be increased if other bone marrow depressants are used with sulfamethoxazole; trimethoprim, SMX-TMP, cotrimoxazole. Megaloblastic anemia can occur when sulfamethoxazole; trimethoprim, SMX-TMP is used in patients who are taking other folate antagonists. These agents include: valproic acid, divalproex sodium. If these agents are used concomitantly, close observation of blood counts is warranted. (Minor) Use of other folate antagonists should be avoided during therapy with trimethoprim. Hematologic toxicity can be increased by concurrent use of divalproex or valproic acid.
    Valsartan: (Moderate) Monitor for hyperkalemia if concomitant use of an angiotensin II receptor antagonist and trimethoprim is necessary. For those patients at higher risk of hyperkalemia (e.g., the elderly, patients with underlying disorders of potassium metabolism, and those with renal dysfunction), consideration of an alternate antibiotic may be warranted. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in those with pre-existing risk factors.
    Vandetanib: (Major) The manufacturer of vandetanib recommends avoiding coadministration with other drugs that prolong the QT interval due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib; prolongation of the QT interval, ventricular tachycardia and TdP have been reported during postmarketing use of sulfamethoxazole; trimethoprim. If coadministration is necessary, an ECG is needed, as well as more frequent monitoring of the QT interval. If QTcF is greater than 500 msec, interrupt vandetanib dosing until the QTcF is less than 450 msec; then, vandetanib may be resumed at a reduced dose.
    Vardenafil: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include vardenafil.
    Vemurafenib: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include vemurafenib.
    Verteporfin: (Moderate) Use photosensitizing agents 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.
    Vigabatrin: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as sulfamethoxazole, may occur during concurrent use of vigabatrin.
    Voriconazole: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Concurrent use with other QT prolonging drugs, such as voriconazole, should be done cautiously and with close monitoring. There is also a theoretical CYP2C9 interaction as voriconazole is a substrate of the isoenzyme and sulfamethoxazole is an inhibitor; elevated voriconazole concentrations and, thus, adverse reactions may result.
    Vorinostat: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include vorinostat.
    Warfarin: (Major) Sulfonamides, including sulfamethizole, sulfamethoxazole, and sulfisoxazole, may potentiate the anticoagulant effect of warfarin. Sulfonamides are known to inhibit the hepatic metabolism of the 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. Most of the reported cases of an interaction between warfarin and a sulfonamide drug involved the combination of sulfamethoxazole and trimethoprim, which may be due to the additive effects of trimethoprim mediated CYP2C8 inhibition of warfarin metabolism. Among older patients receiving long-term warfarin therapy, recent sulfamethoxazole; trimethoprim use (i.e., within 14 days) was associated with an increased risk of hospitalization for upper GI bleed (adjusted OR 3.84; 95% CI 2.33-6.33) compared to other antibiotics commonly used for the treatment of UTI (amoxicillin, ampicillin, nitrofurantoin, and norfloxacin). Due to the potential severity of excessive anticoagulation, sulfonamides should be administered cautiously to a patient already stabilized on warfarin. Warfarin doses may need to be adjusted when sulfonamide therapy is discontinued. (Major) Trimethoprim can inhibit the metabolism of warfarin, increasing anticoagulant activity and increasing the risk of developing hematological side effects.
    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. (Moderate) Concomitant use of trimethoprim and zidovudine may result in additive hematological abnormalities. Use caution and monitor for hematologic toxicity during concurrent use.
    Ziprasidone: (Severe) Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). QT prolongation resulting in ventricular tachycardia and TdP have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Because of the potential for TdP, concurrent use is contraindicated.

    PREGNANCY AND LACTATION

    Pregnancy

    Sulfamethoxazole; trimethoprim may cause fetal harm if administered during pregnancy. Use sulfamethoxazole; trimethoprim during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data have linked first trimester exposure to sulfamethoxazole; trimethoprim to an increased risk for congenital malformations (i.e., cardiovascular malformations, neural tube defects, oral cleft, urinary tract defects, club foot). In addition, sulfonamides are considered by some experts to be higher risk when used near term due to the potential for jaundice, hemolytic anemia, and kernicterus in the newborn; sulfonamides readily cross the placenta with fetal concentrations averaging 70% to 90% of maternal concentrations. 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. If sulfamethoxazole; trimethoprim is used during pregnancy, the patient should be advised of the potential risk to the fetus and supplemental multivitamins should be administered. Use of the drug is recommended for prophylaxis of pneumocystis pneumonia (PCP) in HIV-infected pregnant women.

    Both sulfamethoxazole and trimethoprim are excreted into human breast milk at concentrations of approximately 2% to 5% of the recommended daily dose for infants over 2 months of age. Because of the potential risk of bilirubin displacement and kernicterus, avoid breast-feeding during treatment with sulfamethoxazole; trimethoprim. However, previous American Academy of Pediatrics (AAP) recommendations considered sulfamethoxazole; trimethoprim as usually compatible with breast-feeding. An extensive review in HIV-infected women suggested that the risk of kernicterus in the breast-feeding infant is very low. In a study of 12 newborn infants of less than 3 days postnatal age receiving systemic sulfamethoxazole; trimethoprim, the authors noted that despite therapeutic serum concentrations, there was no displacement of bilirubin from albumin in the newborns. If sulfamethoxazole; trimethoprim is administered to the mother of a young infant, monitor the infant for signs of increased bilirubin and jaundice. Ciprofloxacin, amoxicillin, and nitrofurantoin (cautioned in the infant with glucose-6-phosphate dehydrogenase deficiency) may be potential alternatives to consider during breast-feeding as generally considered compatible by previous AAP recommendations.

    MECHANISM OF ACTION

    Sulfamethoxazole; Trimethoprim is usually bactericidal and acts by inhibiting sequential enzymes of the folic acid-synthesis pathway. Sulfamethoxazole is a structural analog of p-aminobenzoic acid (PABA), and it inhibits the formation of dihydrofolic acid by competing with PABA for binding to bacterial dihydropteroate synthase. This action interferes with the conversion of PABA into folic acid, an essential component of bacterial development. Trimethoprim binds to and reversibly inhibits the enzyme dihydrofolate reductase, which prevents the formation of tetrahydrofolic acid from dihydrofolic acid. Tetrahydrofolic acid, or THF, is the metabolically active form of folic acid. Without THF, bacteria cannot synthesize thymidine, which leads to interference with bacterial nucleic acid and protein formation. The combination of trimethoprim with sulfamethoxazole is synergistic against some bacteria.
     
    Differences in toxicity between healthy individuals and certain patient populations has been documented with sulfonamides. Sulfonamides are metabolized mainly by acetylation. Patients who are slow acetylators (50% of the US population) metabolize more sulfonamide drug by the cytochrome P-450 system than fast acetylators. Metabolism via the cytochrome P-450 system produces reactive metabolites, usually detoxified by scavengers, such as glutathione. Some patient populations, however, have low amounts of glutathione (i.e., AIDS patients) and toxic metabolites accumulate, leading to a higher incidence of severe toxicities such as hypersensitivity reactions.

    PHARMACOKINETICS

    Sulfamethoxazole; trimethoprim is administered orally and intravenously.
     
    Sulfamethoxazole is widely distributed throughout all body tissues and fluids, including peritoneal, synovial, pleural, and ocular fluids as well as breast milk. It also crosses the placenta. Trimethoprim is quickly and widely distributed to tissues and fluids. It also enters the bile, aqueous humor, and bone marrow. CSF concentrations are 30—50% of serum concentrations, and high concentrations are reached in prostatic tissue; prostatic fluid; renal, urinary, and pulmonary tissue; and vaginal fluid. It crosses the placenta and enters breast milk. Protein-binding is 44% for trimethoprim and 70% for sulfamethoxazole. In circulation, CYP2C9 metabolizes sulfamethoxazole to form the N4-hydroxy metabolite. Four other sulfamethoxazole metabolites have also been identified: N4-acetyl-, 5-methylhydroxy-, N4-acetyl-5-methylhydroxy-, and the N-glucuronide conjugate. The acetylated metabolites of sulfamethoxazole are more highly bound to protein than is the free drug. Trimethoprim is metabolized into 11 different metabolites, with the major metabolites being the 1- and 3-oxides and the 3- and 4-hydroxy derivatives. Of note, only the free forms of sulfamethoxazole and trimethoprim are considered to be therapeutically active.
     
    The kidney and liver are both important in the elimination of trimethoprim and sulfamethoxazole. Up to 80% of trimethoprim and roughly 20% of sulfamethoxazole are eliminated unchanged in the urine. Both compounds are removed by glomerular filtration, with some tubular secretion. Sulfamethoxazole is also reabsorbed, and its excretion is increased in alkaline urine. Trimethoprim's excretion is increased in acid urine and decreased in alkaline urine. In patients with normal renal function, sulfamethoxazole's half-life ranges from 6—12 hours and trimethoprim's half-life ranges from 8—10 hours. Small amounts of both trimethoprim and sulfamethoxazole are excreted in feces and bile.
     
    Affected cytochrome P450 isoenzymes and drug transporter: CYP2C9, CYP2C8, P-gp, OCT1, OCT2
    Sulfamethoxazole is a substrate and inhibitor of CYP2C9. In vitro data suggest trimethoprim is a substrate for the drug transporters P-glycoprotein (P-gp), OCT1, and OCT2. Trimethoprim also inhibits both OCT2 and the hepatic isoenzyme CYP2C8.

    Oral Route

    Sulfamethoxazole; trimethoprim is rapidly and well absorbed (90—100%) from the GI tract. Peak serum concentrations of 1—2 mcg/ml and 40—60 mcg/ml are achieved 1—4 hours after a single oral dose of 160 mg trimethoprim and 800 mg sulfamethoxazole, respectively. Steady-state peak serum concentrations are 50% greater than this following multiple oral doses. At steady state, the serum ratio of trimethoprim to sulfamethoxazole is 1:20.

    Intravenous Route

    After IV infusion of 160 mg trimethoprim and 800 mg sulfamethoxazole, peak steady-state serum concentrations are roughly 9 mcg/ml and 105 mcg/ml, and troughs are 6 mcg/ml and 70 mcg/ml, respectively.