trimethoprim/sulfamethoxazole (Rx)

Dosing Guidelines for Infections

1-2 DS tablets PO q12-24hr

8-20 mg TMP/kg/day IV q6-12hr  

Chronic Bronchitis

Acute exacerbations of chronic bronchitis due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae

DS tablet: 1 PO q12h for 10-14 days

Meningitis, Bacterial

10-20 mg TMP/kg/day IV divided q6-12hr  

Pneumocystis (Carinii) Jiroveci Pneumonia

Documented Pneumocystis jiroveci pneumonia (PCP); also, prophylaxis against PCP in individuals who are immunosuppressed

Prophylaxis

• Tablet: 80-160 mg TMP PO qDay or 160 mg TMP 3 times/week on consecutive or alternate days

Treatment

• 15-20 mg TMP/kg/day PO/IV divided q6-8hr  

Sepsis

20 mg TMP/kg/day IV divided q6hr  

Shigellosis

Enteritis caused by susceptible strains of Shigella flexneri and S sonnei

DS tablet: 1 tab PO q12hr for 5 days

Alternatively, 8-10 mg TMP/kg/day IV divided q6-12hr for up to 5 days  

Traveler's Diarrhea

Traveler's diarrhea due to susceptible strains of enterotoxigenic Escherichia coli

DS tablet: 1 tab PO q12hr for 5 days

Urinary Tract Infections

UTIs caused by susceptible strains of Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis, and Proteus vulgaris

Pyelonephritis: 1 DS tab or 2 regular-strength tabs PO q12hr x 14 days

Prostatitis: 1 DS tab or 2 regular-strength tabs PO q12hr x 14 days or 2-3 months if chronic infection

A 3 to 5 day course may be used for acute, uncomplicated cystitis

Prophylaxis (off-label): Various regimens exist; may use regular-strength tablet once/twice per week

Acne Vulgaris (Off-label)

1 DS tab or 1 regular-strength tab PO qDay or q12hr for up to 18 weeks

Community Acquired Pneumonia (Off-label)

1 DS tab PO q12hr for 10-14 days

Dosage Modifications

Renal impairment

• CrCl >30 mL/min: Dose adjustment not necessary
• CrCl 15-30 mL/min: Decrease dose by 50%
• CrCl <15 mL/min: Do not use

Renal impairment, off-label

• Administer doses PO/IV
• Dosing (Dose based on Total Body Weight(TBW) and trimethoprim component; use TBW in obese patients)

• Pneumocystis jjirovecii pneumonia (PJP) prophylaxis

  • CrCl < 30mL/min: 160 mg (1DS) q24hr or 80 mg (1 SS) q24hr or 160 mg (1DS) 3x week
  • Hemodialysis (HD): 80 mg (1 SS) q24 hr or 160 mg (1DS) 3 x week; on hemodialysis days, administer dose post-HD
  • Continuous renal replacement therapy (CRRT): 160 mg (1 DS) q24hr or 80 mg (1SS) q24hr or 160 mg (1DS) 3x week

• Pneumocystis jjirovecii pneumonia (PJP) treatment

  • CrCl < 30mL/min: 5 mg/kg q12hr
  • HD: 10 mg/kg post-HD
  • CRRT: 5 mg/kg q12hr
  • Total daily dose: 15-20 mg/kg/day for Pneumocystis treatment

• Skin and soft tissue infection

  • CrCl < 30mL/min: 80-160 mg (1-2 SS) q12hr
  • HD: 80 mg (1SS) q24hr; on hemodialysis days, administer dose post-HD
  • CRRT: 80-160 mg (1-2SS) q12hr

• Stenotrophomonas treatment

  • CrCl<30mL/min: 4 mg/kg q12hr
  • HD: 8 mg/kg post-HD
  • CRRT: 4 mg/kg q12hr
  • Total daily dose: 12-15 mg/kg/day for Stenotrophomonas treatment

• Urinary tract infection

  • CrCl < 30mL/min: 80 mg (1SS) q12hr
  • HD: 80 mg (1SS) q12hr; on hemodialysis days, administer dose post-HD
  • CRRT: 160 mg (1DS) q12hr

• Other Infections

  • CrCl < 30mL/min: 3 mg/kg q12hr
  • HD: 6 mg/kg post-HD
  • CRRT: 3 mg/kg q12hr
  • Total daily dose: 8-12 mg/kg/day

Dosing Considerations

Susceptible organisms

• Acinetobacter baumannii, Actinobacillus actinomycetemcomitans, Aeromonas hydrophila, Alcaligenes xylosoxidans, Bartonella henselae, Bordetella pertussis, Brucella spp, Burkholderia pseudomallei, Burkholderia cepacia, Chryseobacterium meningosepticum, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus aphrophilus, Haemophilus influenzae, Hafnia alvei, Kingella spp, Klebsiella pneumoniae, Klebsiella granulomatis, Legionella spp, Listeria monocytogenes, Moraxella catarrhalis, Morganella morganii, MRSA, MSSA, Nocardia asteroides, Plesiomonas shigelloides, Pneumocystis jiroveci (PCP), Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Salmonella typhi, Serratia spp, Shigella spp, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus pneumoniae, Tropheryma whippelii, Vibrio cholerae, Yersinia enterocolitica, Yersinia pseudotuberculosis, various Mycobacteria

Mild to Moderate Infections

<2 months: Contraindicated

>2 months

• 8 mg TMP/kg/day PO divided q12hr  

Serious Infections

<2 months: Contraindicated

>2 months

• 15-20 mg TMP/kg qDay PO divided q6hr  
• 8-12 mg TMP/kg/day IV divided q6-12hr

Acute Otitis Media

Acute otitis media in pediatric patients due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae

<2 months: Contraindicated

>2 months: 6-10 mg TMP/kg/day PO divided q12hr for 10 days  

Pneumocystis (Carinii) Jiroveci Pneumonia

<2 months: Contraindicated

>2 months

• Treatment: 15-20 mg TMP/kg/day PO/IV divided q6-8hr for 21 days  
• Prophylaxis: 150 mg TMP/m²/day PO divided q12 hr for 3 days/week on consecutive or alternate days  

Shigellosis

<2 months: Contraindicated

>2 months

• 8 mg TMP/kg/day PO divided q12hr for 5 days  
• 8-10 mg TMP/kg/day IV divided q6-12hr for 5 days

Urinary Tract Infection

<2 months: Contraindicated

>2 months

• 8 mg TMP/kg/day PO divided q12hr for 7-14 days if serious infection  
• 8-10 mg TMP/kg/day IV divided q6-12hr for 14 days if serious infection
• Prophylaxis: 2 mg TMP/kg/dose PO qDay or 5 mg TMP/kg/dose twice weekly

Skin/soft Tissue Infection Due to Community Acquired MRSA (Off-label)

8-12 mg TMP/kg/day PO divided q12hr for 5-10 days; add beta-lactam antibiotic to regimen if beta-hemolytic Streptococcus spp also suspected  

Contraindicated (0)

Serious - Use Alternative (56)

• abametapir

  abametapir will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

• aminobenzoate potassium

  aminobenzoate potassium decreases effects of sulfamethoxazole by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• aminolevulinic acid oral

  aminolevulinic acid oral, sulfamethoxazole. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

• aminolevulinic acid topical

  sulfamethoxazole, aminolevulinic acid topical. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• amiodarone

  amiodarone and sulfamethoxazole both increase QTc interval. Avoid or Use Alternate Drug.
  
  amiodarone and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.

• antithrombin alfa

  sulfamethoxazole increases effects of antithrombin alfa by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of antithrombin alfa by plasma protein binding competition. Avoid or Use Alternate Drug.

• BCG vaccine live

  trimethoprim decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.

• apalutamide

  apalutamide will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• antithrombin III

  sulfamethoxazole increases effects of antithrombin III by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of antithrombin III by plasma protein binding competition. Avoid or Use Alternate Drug.

• argatroban

  sulfamethoxazole increases effects of argatroban by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of argatroban by plasma protein binding competition. Avoid or Use Alternate Drug.

• BCG vaccine live

  sulfamethoxazole decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.

• bemiparin

  sulfamethoxazole increases effects of bemiparin by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of bemiparin by plasma protein binding competition. Avoid or Use Alternate Drug.

• bivalirudin

  sulfamethoxazole increases effects of bivalirudin by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of bivalirudin by plasma protein binding competition. Avoid or Use Alternate Drug.

• cholera vaccine

  trimethoprim, cholera vaccine. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid coadministration of cholera vaccine with systemic antibiotics since these agents may be active against the vaccine strain. Do not administer cholera vaccine to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination.

• dalteparin

  sulfamethoxazole increases effects of dalteparin by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of dalteparin by plasma protein binding competition. Avoid or Use Alternate Drug.

• disopyramide

  disopyramide and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.
  
  sulfamethoxazole and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.

• enoxaparin

  sulfamethoxazole increases effects of enoxaparin by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of enoxaparin by plasma protein binding competition. Avoid or Use Alternate Drug.

• erdafitinib

  trimethoprim will increase the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. If coadministration of a strong CYP2C9 inhibitors is unavoidable, closely monitor adverse reactions and modify dose of erdafitinib accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

• erdafitinib

  sulfamethoxazole will increase the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with strong CYP2C9 inhibitors, monitor closely for adverse reactions and consider decreasing dose accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

• fexinidazole

  fexinidazole will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fondaparinux

  sulfamethoxazole increases effects of fondaparinux by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of fondaparinux by plasma protein binding competition. Avoid or Use Alternate Drug.

• heparin

  sulfamethoxazole increases effects of heparin by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of heparin by plasma protein binding competition. Avoid or Use Alternate Drug.

• ibutilide

  ibutilide and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.
  
  sulfamethoxazole and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.

• idelalisib

  idelalisib will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

• indapamide

  sulfamethoxazole and indapamide both increase QTc interval. Avoid or Use Alternate Drug.

• indapamide

  indapamide and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.

• ivosidenib

  ivosidenib will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
  
  ivosidenib will decrease the level or effect of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• leucovorin

  leucovorin decreases effects of trimethoprim by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Monitor for trimethoprim treatment failure or decreased efficacy when coadministered with leucovorin, especially when used with sulfamethoxazole for Pneumocystis jiroveci pneumonia in patients who are HIV positive .

• levoleucovorin

  levoleucovorin decreases effects of trimethoprim by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Monitor for trimethoprim treatment failure or decreased efficacy when coadministered with levoleucovorin, especially when used with sulfamethoxazole for Pneumocystis jiroveci pneumonia in patients who are HIV positive .

• lonafarnib

  lonafarnib will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

• lopinavir

  lopinavir will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• mefloquine

  mefloquine increases toxicity of trimethoprim by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.
  
  mefloquine increases toxicity of sulfamethoxazole by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.

• methenamine

  methenamine, sulfamethoxazole. Other (see comment). Contraindicated. Comment: This combination may form an insoluble precipitate in the urine, decreasing the effects of both agents.

• methotrexate

  trimethoprim, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Due to an additive antifolate effect, trimethoprim has been shown to rarely increase bone marrow suppression in patients receiving methotrexate.

• methotrexate

  sulfamethoxazole increases toxicity of methotrexate by plasma protein binding competition. Avoid or Use Alternate Drug. Methotrexate concentrations may be elevated, increasing the risk of toxicity (eg, bone marrow suppression).

• methyl aminolevulinate

  sulfamethoxazole, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• microbiota oral

  trimethoprim decreases effects of microbiota oral by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Microbiota oral contains bacterial spores. Antibacterial agents may decrease efficacy if coadministered. Complete antibiotic regimens 2-4 days before initiating microbiota oral. .

• pentamidine

  sulfamethoxazole and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.
  
  pentamidine and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.

• pexidartinib

  sulfamethoxazole and pexidartinib both increase inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

• pimozide

  pimozide and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.

• phenindione

  sulfamethoxazole increases effects of phenindione by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of phenindione by plasma protein binding competition. Avoid or Use Alternate Drug.

• pimozide

  sulfamethoxazole and pimozide both increase QTc interval. Avoid or Use Alternate Drug.

• pretomanid

  sulfamethoxazole, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

• procainamide

  sulfamethoxazole and procainamide both increase QTc interval. Avoid or Use Alternate Drug.
  
  procainamide and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.

• protamine

  sulfamethoxazole increases effects of protamine by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of protamine by plasma protein binding competition. Avoid or Use Alternate Drug.

• quinidine

  quinidine and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.

• quinidine

  quinidine and sulfamethoxazole both increase QTc interval. Avoid or Use Alternate Drug.

• siponimod

  trimethoprim will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.
  
  sulfamethoxazole will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

• sotalol

  sulfamethoxazole and sotalol both increase QTc interval. Avoid or Use Alternate Drug.
  
  sotalol and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.

• tafenoquine

  tafenoquine will increase the level or effect of trimethoprim by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.

• tretinoin

  sulfamethoxazole, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• tretinoin topical

  sulfamethoxazole, tretinoin topical. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• trilaciclib

  trilaciclib will decrease the level or effect of trimethoprim by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.

• tucatinib

  trimethoprim will increase the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inhibitors increases tucatinib plasma concentrations and risk of toxicities.
  
  tucatinib will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• typhoid vaccine live

  sulfamethoxazole decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.
  
  trimethoprim decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.

• voxelotor

  voxelotor will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

Monitor Closely (192)

• aliskiren

  trimethoprim and aliskiren both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• alpelisib

  alpelisib will decrease the level or effect of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• amantadine

  trimethoprim increases levels of amantadine by decreasing elimination. Use Caution/Monitor. Coadministration may impair renal clearance of amantadine, resulting in higher plasma concentrations.
  
  sulfamethoxazole increases levels of amantadine by decreasing elimination. Use Caution/Monitor. Coadministration may impair renal clearance of amantadine, resulting in higher plasma concentrations.

• amiloride

  trimethoprim and amiloride both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• amiodarone

  amiodarone will increase the level or effect of sulfamethoxazole by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• amiodarone

  amiodarone will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• amitriptyline

  amitriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• amoxapine

  amoxapine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amoxapine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• apalutamide

  apalutamide will decrease the level or effect of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Coadministration of apalutamide, a weak CYP2C9 inducer, with drugs that are CYP2C9 substrates can result in lower exposure to these medications. Evaluate for loss of therapeutic effect if medication must be coadministered.

• artemether/lumefantrine

  sulfamethoxazole and artemether/lumefantrine both increase QTc interval. Modify Therapy/Monitor Closely.

• artemether/lumefantrine

  artemether/lumefantrine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• aspirin

  aspirin, sulfamethoxazole. Either increases effects of the other by plasma protein binding competition. Use Caution/Monitor. Due to high protein binding capacity of both drugs, one may displace the other when coadministered leading to an enhanced effect of the displaced drug; risk is low with low dose aspirin.

• aspirin/citric acid/sodium bicarbonate

  aspirin/citric acid/sodium bicarbonate, sulfamethoxazole. Either increases effects of the other by plasma protein binding competition. Use Caution/Monitor. Due to high protein binding capacity of both drugs, one may displace the other when coadministered leading to an enhanced effect of the displaced drug; risk is low with low dose aspirin.

• bazedoxifene/conjugated estrogens

  sulfamethoxazole will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  trimethoprim will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• benazepril

  trimethoprim and benazepril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• carvedilol

  sulfamethoxazole will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• canagliflozin

  trimethoprim and canagliflozin both increase serum potassium. Use Caution/Monitor.

• candesartan

  trimethoprim and candesartan both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• cannabidiol

  cannabidiol will increase the level or effect of trimethoprim by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

• captopril

  trimethoprim and captopril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• chlorpromazine

  chlorpromazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  chlorpromazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• chlorpropamide

  sulfamethoxazole increases levels of chlorpropamide by plasma protein binding competition. Use Caution/Monitor.

• cimetidine

  cimetidine will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• cimetidine

  cimetidine will increase the level or effect of sulfamethoxazole by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• clarithromycin

  clarithromycin and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  clarithromycin and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• clomipramine

  clomipramine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  clomipramine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• conjugated estrogens

  trimethoprim will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  sulfamethoxazole will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• crofelemer

  crofelemer increases levels of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• cyclosporine

  sulfamethoxazole, cyclosporine. Either increases effects of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

• cyclosporine

  trimethoprim and cyclosporine both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• dabrafenib

  dabrafenib will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dapsone topical

  trimethoprim increases toxicity of dapsone topical by decreasing metabolism. Modify Therapy/Monitor Closely. Coadministration increases systemic exposure of dapsone and its metabolites (N-acetyl-dapsone, dapsone hydroxylamine). May induce methemoglobinemia.
  
  sulfamethoxazole increases toxicity of dapsone topical by decreasing metabolism. Modify Therapy/Monitor Closely. Coadministration increases systemic exposure of dapsone and its metabolites (N-acetyl-dapsone, dapsone hydroxylamine). May induce methemoglobinemia.

• desipramine

  desipramine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  desipramine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• digoxin

  digoxin will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  sulfamethoxazole will increase the level or effect of digoxin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  trimethoprim will increase the level or effect of digoxin by altering intestinal flora. Applies only to oral form of both agents. Use Caution/Monitor.
  
  sulfamethoxazole will increase the level or effect of digoxin by altering intestinal flora. Applies only to oral form of both agents. Use Caution/Monitor.

• dofetilide

  dofetilide and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole will increase the level or effect of dofetilide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  dofetilide will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  sulfamethoxazole and dofetilide both increase QTc interval. Modify Therapy/Monitor Closely.

• dolasetron

  sulfamethoxazole and dolasetron both increase QTc interval. Use Caution/Monitor.
  
  dolasetron and trimethoprim both increase QTc interval. Use Caution/Monitor.

• doxepin

  doxepin and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  doxepin and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• dronabinol

  sulfamethoxazole will increase the level or effect of dronabinol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dronabinol is a CYP2C9 substrate.

• dronedarone

  dronedarone and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• dronedarone

  sulfamethoxazole and dronedarone both increase QTc interval. Modify Therapy/Monitor Closely.

• droperidol

  droperidol and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and droperidol both increase QTc interval. Modify Therapy/Monitor Closely.

• efavirenz

  efavirenz will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• elagolix

  elagolix decreases levels of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• eltrombopag

  sulfamethoxazole will increase the level or effect of eltrombopag by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• eluxadoline

  sulfamethoxazole increases levels of eluxadoline by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP2C9/10 inhibitors.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF decreases levels of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Elvitegravir is a moderate CYP2C9 inducer.

• enalapril

  trimethoprim and enalapril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• encorafenib

  encorafenib, trimethoprim. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• epinephrine

  epinephrine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  epinephrine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• epinephrine racemic

  epinephrine racemic and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  epinephrine racemic and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• eplerenone

  trimethoprim and eplerenone both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• erythromycin base

  sulfamethoxazole and erythromycin base both increase QTc interval. Modify Therapy/Monitor Closely.

• eprosartan

  trimethoprim and eprosartan both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• erdafitinib

  erdafitinib increases levels of trimethoprim by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.

• erythromycin base

  erythromycin base and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• erythromycin ethylsuccinate

  sulfamethoxazole and erythromycin ethylsuccinate both increase QTc interval. Modify Therapy/Monitor Closely.
  
  erythromycin ethylsuccinate and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• erythromycin lactobionate

  erythromycin lactobionate and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and erythromycin lactobionate both increase QTc interval. Modify Therapy/Monitor Closely.

• erythromycin stearate

  sulfamethoxazole and erythromycin stearate both increase QTc interval. Modify Therapy/Monitor Closely.
  
  erythromycin stearate and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• estradiol

  trimethoprim will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  sulfamethoxazole will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• estrogens conjugated synthetic

  trimethoprim will decrease the level or effect of estrogens conjugated synthetic by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  sulfamethoxazole will decrease the level or effect of estrogens conjugated synthetic by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• estropipate

  trimethoprim will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  sulfamethoxazole will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• ethinylestradiol

  trimethoprim will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  sulfamethoxazole will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• ethotoin

  sulfamethoxazole will increase the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• fedratinib

  fedratinib will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• etravirine

  sulfamethoxazole will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• finerenone

  trimethoprim and finerenone both increase serum potassium. Modify Therapy/Monitor Closely. Finerenone dose adjustment based on current serum potassium concentration. Monitor serum potassium and adjust finerenone dose as described in the prescribing information as necessary.

• flecainide

  sulfamethoxazole and flecainide both increase QTc interval. Use Caution/Monitor.
  
  flecainide and trimethoprim both increase QTc interval. Use Caution/Monitor.

• fluconazole

  fluconazole and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and fluconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• fluoxetine

  fluoxetine and trimethoprim both increase QTc interval. Use Caution/Monitor.
  
  fluoxetine will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• fluphenazine

  fluphenazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  fluphenazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• fluvoxamine

  fluvoxamine and trimethoprim both increase QTc interval. Use Caution/Monitor.
  
  fluvoxamine and sulfamethoxazole both increase QTc interval. Use Caution/Monitor.

• formoterol

  sulfamethoxazole and formoterol both increase QTc interval. Modify Therapy/Monitor Closely.
  
  formoterol and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• foscarnet

  sulfamethoxazole and foscarnet both increase QTc interval. Use Caution/Monitor.
  
  foscarnet and trimethoprim both increase QTc interval. Use Caution/Monitor.

• fosinopril

  trimethoprim and fosinopril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• fosphenytoin

  sulfamethoxazole will increase the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• fosphenytoin

  fosphenytoin will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• glimepiride

  sulfamethoxazole increases levels of glimepiride by plasma protein binding competition. Use Caution/Monitor.

• glipizide

  sulfamethoxazole increases levels of glipizide by plasma protein binding competition. Use Caution/Monitor.

• glucarpidase

  glucarpidase will decrease the level or effect of sulfamethoxazole by increasing metabolism. Modify Therapy/Monitor Closely. Leucorvorin, reduced folates, and folate antimetabolites are substrates for glucarpidase (hydrolyzes glutamate residue from folic acid and antifolates)
  
  glucarpidase will decrease the level or effect of trimethoprim by increasing metabolism. Modify Therapy/Monitor Closely. Leucorvorin, reduced folates, and folate antimetabolites are substrates for glucarpidase (hydrolyzes glutamate residue from folic acid and antifolates)

• glyburide

  sulfamethoxazole increases levels of glyburide by plasma protein binding competition. Use Caution/Monitor.
  
  sulfamethoxazole increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

• haloperidol

  haloperidol and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• haloperidol

  sulfamethoxazole and haloperidol both increase QTc interval. Modify Therapy/Monitor Closely.

• iloperidone

  sulfamethoxazole and iloperidone both increase QTc interval. Use Caution/Monitor.
  
  iloperidone and trimethoprim both increase QTc interval. Use Caution/Monitor.
  
  iloperidone increases levels of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

• imatinib

  imatinib will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• imipramine

  imipramine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• imidapril

  sulfamethoxazole, imidapril. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• imipramine

  imipramine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• indinavir

  indinavir will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• irbesartan

  trimethoprim and irbesartan both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• istradefylline

  istradefylline will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• itraconazole

  sulfamethoxazole and itraconazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  itraconazole and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• ketoconazole

  ketoconazole and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• L-methylfolate

  trimethoprim decreases effects of L-methylfolate by Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Folic acid antagonists may interfere with folic acid utilization.

• lacosamide

  sulfamethoxazole increases levels of lacosamide by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Consider decreasing lacosamide dose when coadministered with strong CYP2C9 inhibitors.

• lamivudine

  trimethoprim increases effects of lamivudine by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor. Potential for increased toxicity.

• lapatinib

  sulfamethoxazole and lapatinib both increase QTc interval. Use Caution/Monitor.

• lenacapavir

  lenacapavir will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• lesinurad

  sulfamethoxazole will increase the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• levofloxacin

  sulfamethoxazole and levofloxacin both increase QTc interval. Use Caution/Monitor.
  
  levofloxacin and trimethoprim both increase QTc interval. Use Caution/Monitor.

• levoketoconazole

  levoketoconazole and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and levoketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  trimethoprim will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.
  
  sulfamethoxazole will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.

• lisinopril

  trimethoprim and lisinopril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• lofepramine

  lofepramine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• lofepramine

  lofepramine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• losartan

  sulfamethoxazole will increase the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. May inhibit the conversion of losartan to its active metabolite E-3174. Importance of interaction not established; monitor individual therapeutic response to determine losartan dosage.
  
  trimethoprim and losartan both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• lumacaftor/ivacaftor

  lumacaftor/ivacaftor, trimethoprim. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• lumefantrine

  sulfamethoxazole and lumefantrine both increase QTc interval. Modify Therapy/Monitor Closely.

• lumefantrine

  lumefantrine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• maprotiline

  maprotiline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  maprotiline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• mestranol

  trimethoprim will decrease the level or effect of mestranol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  sulfamethoxazole will decrease the level or effect of mestranol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• metformin

  trimethoprim increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Trimethoprim may inhibit active renal tubular secretion of metformin (eg, via OCT2, MATE1); dose adjustments may be necessary.

• methadone

  sulfamethoxazole and methadone both increase QTc interval. Use Caution/Monitor.

• methadone

  methadone and trimethoprim both increase QTc interval. Use Caution/Monitor.

• methotrexate

  trimethoprim increases toxicity of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Trimethoprim may increase risk of methotrexate-induced bone marrow suppression and megaloblastic anemia. If this drug combination cannot be avoided, closely monitor for signs of hematologic toxicity.

• methoxsalen

  methoxsalen, sulfamethoxazole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

• metronidazole

  metronidazole, sulfamethoxazole. Mechanism: decreasing metabolism. Use Caution/Monitor. Disulfiram like reaction.

• mipomersen

  mipomersen, sulfamethoxazole. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• mitotane

  mitotane decreases levels of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

• moexipril

  trimethoprim and moexipril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• moxifloxacin

  sulfamethoxazole and moxifloxacin both increase QTc interval. Modify Therapy/Monitor Closely.
  
  moxifloxacin and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• nateglinide

  sulfamethoxazole will increase the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  sulfamethoxazole increases levels of nateglinide by plasma protein binding competition. Use Caution/Monitor.

• nitisinone

  nitisinone will increase the level or effect of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

• nilotinib

  sulfamethoxazole and nilotinib both increase QTc interval. Modify Therapy/Monitor Closely.

• nortriptyline

  nortriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  nortriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• octreotide

  octreotide and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and octreotide both increase QTc interval. Modify Therapy/Monitor Closely.

• octreotide (Antidote)

  octreotide (Antidote) and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and octreotide (Antidote) both increase QTc interval. Modify Therapy/Monitor Closely.

• ofloxacin

  sulfamethoxazole and ofloxacin both increase QTc interval. Use Caution/Monitor.
  
  ofloxacin and trimethoprim both increase QTc interval. Use Caution/Monitor.

• olmesartan

  trimethoprim and olmesartan both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• ospemifene

  sulfamethoxazole increases levels of ospemifene by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  sulfamethoxazole, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

• paclitaxel

  trimethoprim will increase the level or effect of paclitaxel by Other (see comment). Use Caution/Monitor. Paclitaxel levels/toxicity may increase when coadministered with CYP2C8 inhibitors

• paclitaxel protein bound

  trimethoprim will increase the level or effect of paclitaxel protein bound by Other (see comment). Use Caution/Monitor. Paclitaxel levels/toxicity may increase when coadministered with CYP2C8 inhibitors

• paliperidone

  sulfamethoxazole and paliperidone both increase QTc interval. Use Caution/Monitor.
  
  paliperidone and trimethoprim both increase QTc interval. Use Caution/Monitor.

• parecoxib

  sulfamethoxazole will increase the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• paroxetine

  paroxetine and trimethoprim both increase QTc interval. Use Caution/Monitor.

• paroxetine

  sulfamethoxazole and paroxetine both increase QTc interval. Use Caution/Monitor.

• pentamidine

  trimethoprim and pentamidine both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• perindopril

  trimethoprim and perindopril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• perphenazine

  perphenazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• phenytoin

  sulfamethoxazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• posaconazole

  posaconazole and trimethoprim both increase QTc interval. Use Caution/Monitor.

• porfimer

  sulfamethoxazole, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

• posaconazole

  sulfamethoxazole and posaconazole both increase QTc interval. Use Caution/Monitor.

• potassium acid phosphate

  trimethoprim and potassium acid phosphate both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• potassium chloride

  trimethoprim and potassium chloride both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• potassium citrate

  trimethoprim and potassium citrate both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• potassium citrate/citric acid

  trimethoprim and potassium citrate/citric acid both increase serum potassium. Use Caution/Monitor.

• pralatrexate

  sulfamethoxazole increases levels of pralatrexate by decreasing renal clearance. Use Caution/Monitor.

• procainamide

  sulfamethoxazole will increase the level or effect of procainamide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  procainamide will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• prochlorperazine

  prochlorperazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  prochlorperazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• promazine

  promazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  promazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  promazine increases toxicity of sulfamethoxazole by unspecified interaction mechanism. Use Caution/Monitor. Enhanced myelosuppression.

• promethazine

  promethazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  promethazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• protriptyline

  protriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  protriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• quinapril

  trimethoprim and quinapril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• quinidine

  quinidine will increase the level or effect of sulfamethoxazole by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• quinidine

  quinidine will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

• ramipril

  trimethoprim and ramipril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• ranolazine

  sulfamethoxazole and ranolazine both increase QTc interval. Use Caution/Monitor.
  
  ranolazine and trimethoprim both increase QTc interval. Use Caution/Monitor.

• repaglinide

  trimethoprim increases levels of repaglinide by decreasing metabolism. Use Caution/Monitor. Hepatic cytochrome P450 2C8.
  
  sulfamethoxazole increases levels of repaglinide by plasma protein binding competition. Use Caution/Monitor.

• rifabutin

  rifabutin will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• risperidone

  sulfamethoxazole and risperidone both increase QTc interval. Use Caution/Monitor.

• rifampin

  rifampin will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• risperidone

  risperidone and trimethoprim both increase QTc interval. Use Caution/Monitor.

• sacubitril/valsartan

  sacubitril/valsartan and trimethoprim both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• selexipag

  trimethoprim will increase the level or effect of selexipag by decreasing metabolism. Modify Therapy/Monitor Closely. Reduce selexipag dose to once daily if coadministered with moderate CYP2C8 inhibitors.

• sodium picosulfate/magnesium oxide/anhydrous citric acid

  trimethoprim decreases effects of sodium picosulfate/magnesium oxide/anhydrous citric acid by altering metabolism. Use Caution/Monitor. Coadministration with antibiotics decreases efficacy by altering colonic bacterial flora needed to convert sodium picosulfate to active drug.
  
  sulfamethoxazole decreases effects of sodium picosulfate/magnesium oxide/anhydrous citric acid by altering metabolism. Use Caution/Monitor. Coadministration with antibiotics decreases efficacy by altering colonic bacterial flora needed to convert sodium picosulfate to active drug.

• sparsentan

  sparsentan will decrease the level or effect of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates.

• tamoxifen

  sulfamethoxazole, tamoxifen. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. CYP2C9/10 inhibition decreases tamoxifen metabolism to active metabolites.

• spironolactone

  trimethoprim and spironolactone both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• sulfamethoxazole

  sulfamethoxazole and trimethoprim both increase QTc interval. Use Caution/Monitor.

• tecovirimat

  tecovirimat will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• telavancin

  telavancin and trimethoprim both increase QTc interval. Use Caution/Monitor.
  
  sulfamethoxazole and telavancin both increase QTc interval. Use Caution/Monitor.

• telmisartan

  trimethoprim and telmisartan both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• terbinafine

  sulfamethoxazole will increase the level or effect of terbinafine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• thioridazine

  thioridazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  thioridazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• tolazamide

  sulfamethoxazole increases levels of tolazamide by plasma protein binding competition. Use Caution/Monitor.

• trandolapril

  trimethoprim and trandolapril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• tolbutamide

  sulfamethoxazole increases levels of tolbutamide by plasma protein binding competition. Use Caution/Monitor.

• trazodone

  trazodone and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  trazodone and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• triamterene

  trimethoprim and triamterene both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• trifluoperazine

  trifluoperazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• trifluoperazine

  trifluoperazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• trimethoprim

  sulfamethoxazole and trimethoprim both increase QTc interval. Use Caution/Monitor.

• trimipramine

  trimipramine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  trimipramine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• tropisetron

  trimethoprim and tropisetron both increase QTc interval. Use Caution/Monitor.
  
  sulfamethoxazole and tropisetron both increase QTc interval. Use Caution/Monitor.

• valsartan

  valsartan and trimethoprim both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• venlafaxine

  sulfamethoxazole and venlafaxine both increase QTc interval. Use Caution/Monitor.

• venlafaxine

  trimethoprim and venlafaxine both increase QTc interval. Use Caution/Monitor.

• voclosporin

  voclosporin and trimethoprim both decrease serum potassium. Use Caution/Monitor.

• voriconazole

  trimethoprim and voriconazole both increase QTc interval. Use Caution/Monitor.
  
  sulfamethoxazole and voriconazole both increase QTc interval. Use Caution/Monitor.

• warfarin

  sulfamethoxazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Mechanism of interaction may be caused by CYP2C9 inhibition and protein-binding displacement. If coadministered, consider decreasing warfarin dose by 10-20%.

• zidovudine

  trimethoprim increases levels of zidovudine by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

• ziprasidone

  sulfamethoxazole and ziprasidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  trimethoprim and ziprasidone both increase QTc interval. Modify Therapy/Monitor Closely.

Minor (137)

• acetazolamide

  acetazolamide will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• alosetron

  sulfamethoxazole will increase the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• amiloride

  amiloride, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  amiloride, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  amiloride increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• aminohippurate sodium

  sulfamethoxazole, aminohippurate sodium. Other (see comment). Minor/Significance Unknown. Comment: This substance interferes with chemical color development of aminohippurate (PAH) essential to accurate renal clearance analysis.

• anastrozole

  anastrozole will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• amiodarone

  amiodarone will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• amitriptyline

  sulfamethoxazole decreases levels of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown.

• amobarbital

  amobarbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• amoxapine

  sulfamethoxazole decreases levels of amoxapine by unspecified interaction mechanism. Minor/Significance Unknown.

• aspirin rectal

  aspirin rectal increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• aspirin/citric acid/sodium bicarbonate

  aspirin/citric acid/sodium bicarbonate increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• azathioprine

  sulfamethoxazole, azathioprine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Leukopenia due to additive myelosuppression.

• azithromycin

  azithromycin and sulfamethoxazole both increase QTc interval. Minor/Significance Unknown.
  
  azithromycin and trimethoprim both increase QTc interval. Minor/Significance Unknown.

• balsalazide

  trimethoprim will decrease the level or effect of balsalazide by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  sulfamethoxazole will decrease the level or effect of balsalazide by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  balsalazide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• bendroflumethiazide

  bendroflumethiazide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  bendroflumethiazide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  bendroflumethiazide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• biotin

  trimethoprim will decrease the level or effect of biotin by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  sulfamethoxazole will decrease the level or effect of biotin by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

• bosentan

  sulfamethoxazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• chlorothiazide

  chlorothiazide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• bumetanide

  bumetanide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• butabarbital

  butabarbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• butalbital

  butalbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• carbamazepine

  carbamazepine will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• celecoxib

  sulfamethoxazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• chlorothiazide

  chlorothiazide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  chlorothiazide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• chlorthalidone

  chlorthalidone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  chlorthalidone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  chlorthalidone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• choline magnesium trisalicylate

  choline magnesium trisalicylate increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• cyclopenthiazide

  cyclopenthiazide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• cimetidine

  cimetidine will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• clomipramine

  sulfamethoxazole decreases levels of clomipramine by unspecified interaction mechanism. Minor/Significance Unknown.

• cyclopenthiazide

  cyclopenthiazide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  cyclopenthiazide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• cyclophosphamide

  cyclophosphamide will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dapsone

  sulfamethoxazole, dapsone. Either increases levels of the other by decreasing elimination. Minor/Significance Unknown.
  
  trimethoprim, dapsone. Either increases levels of the other by decreasing elimination. Minor/Significance Unknown.

• desipramine

  sulfamethoxazole decreases levels of desipramine by unspecified interaction mechanism. Minor/Significance Unknown.

• drospirenone

  drospirenone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.

• diclofenac

  sulfamethoxazole will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• diflunisal

  diflunisal increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• diltiazem

  sulfamethoxazole will increase the level or effect of diltiazem by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• disulfiram

  disulfiram will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• dosulepin

  sulfamethoxazole decreases levels of dosulepin by unspecified interaction mechanism. Minor/Significance Unknown.

• doxepin

  sulfamethoxazole decreases levels of doxepin by unspecified interaction mechanism. Minor/Significance Unknown.

• drospirenone

  drospirenone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  drospirenone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• ethacrynic acid

  ethacrynic acid increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• ethotoin

  sulfamethoxazole increases levels of ethotoin by decreasing metabolism. Minor/Significance Unknown.

• etravirine

  etravirine will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• felbamate

  felbamate will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluconazole

  fluconazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• flurbiprofen

  sulfamethoxazole will increase the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluvastatin

  sulfamethoxazole will increase the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• folic acid

  sulfamethoxazole decreases levels of folic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• fosphenytoin

  sulfamethoxazole increases levels of fosphenytoin by decreasing metabolism. Minor/Significance Unknown.

• furosemide

  furosemide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• ganciclovir

  ganciclovir increases toxicity of sulfamethoxazole by pharmacodynamic synergism. Minor/Significance Unknown.

• hydrochlorothiazide

  hydrochlorothiazide will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  hydrochlorothiazide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  hydrochlorothiazide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  hydrochlorothiazide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  sulfamethoxazole will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ibuprofen

  sulfamethoxazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• indapamide

  indapamide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• ibuprofen IV

  sulfamethoxazole will increase the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• imipramine

  sulfamethoxazole decreases levels of imipramine by unspecified interaction mechanism. Minor/Significance Unknown.

• indapamide

  indapamide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  indapamide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• indomethacin

  indomethacin increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• isavuconazonium sulfate

  isavuconazonium sulfate will increase the level or effect of trimethoprim by Other (see comment). Minor/Significance Unknown. Isavuconazonium sulfate, an OCT2 inhibitor, may increase the effects or levels of OCT2 substrates.

• isocarboxazid

  isocarboxazid increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• ketoconazole

  ketoconazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• L-methylfolate

  sulfamethoxazole decreases levels of L-methylfolate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• lamivudine

  sulfamethoxazole increases levels of lamivudine by decreasing renal clearance. Minor/Significance Unknown.

• larotrectinib

  larotrectinib will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• leflunomide

  leflunomide will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• levoketoconazole

  levoketoconazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  levoketoconazole will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• linezolid

  linezolid increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• memantine

  memantine will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• lofepramine

  sulfamethoxazole decreases levels of lofepramine by unspecified interaction mechanism. Minor/Significance Unknown.

• losartan

  sulfamethoxazole decreases effects of losartan by decreasing metabolism. Minor/Significance Unknown. May inhibit the conversion of losartan to its active metabolite E-3174. Importance of interaction not established; monitor individual therapeutic response to determine losartan dosage.

• maprotiline

  sulfamethoxazole decreases levels of maprotiline by unspecified interaction mechanism. Minor/Significance Unknown.

• meloxicam

  sulfamethoxazole will increase the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• memantine

  sulfamethoxazole will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mesalamine

  mesalamine increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• metformin

  sulfamethoxazole will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  metformin will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methyclothiazide

  methyclothiazide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  methyclothiazide will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  methyclothiazide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  sulfamethoxazole will increase the level or effect of methyclothiazide by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metolazone

  metolazone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  metolazone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  metolazone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• metronidazole

  metronidazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• midodrine

  midodrine will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• miconazole vaginal

  miconazole vaginal will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• midodrine

  sulfamethoxazole will increase the level or effect of midodrine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mineral oil

  mineral oil decreases levels of sulfamethoxazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• nateglinide

  nateglinide will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• nilotinib

  nilotinib will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• nitazoxanide

  nitazoxanide, sulfamethoxazole. Either increases levels of the other by Mechanism: plasma protein binding competition. Minor/Significance Unknown.

• nortriptyline

  sulfamethoxazole decreases levels of nortriptyline by unspecified interaction mechanism. Minor/Significance Unknown.

• ofloxacin

  ofloxacin will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  sulfamethoxazole will increase the level or effect of ofloxacin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• omeprazole

  omeprazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• pantothenic acid

  trimethoprim will decrease the level or effect of pantothenic acid by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

• pantothenic acid

  sulfamethoxazole will decrease the level or effect of pantothenic acid by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

• patiromer

  patiromer, trimethoprim. cation binding in GI tract. Minor/Significance Unknown. No observed clinically important interaction. No separation of dosing required.

• pazopanib

  sulfamethoxazole and pazopanib both increase QTc interval. Minor/Significance Unknown.

• pentobarbital

  pentobarbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• phenelzine

  phenelzine increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• phenobarbital

  phenobarbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• phenytoin

  sulfamethoxazole increases levels of phenytoin by decreasing metabolism. Minor/Significance Unknown.

• pimozide

  sulfamethoxazole decreases levels of pimozide by unspecified interaction mechanism. Minor/Significance Unknown.

• piroxicam

  sulfamethoxazole will increase the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• primaquine

  primaquine, sulfamethoxazole. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hemolysis in G6PD deficient pts.

• primidone

  primidone will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• probenecid

  probenecid increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• protriptyline

  sulfamethoxazole decreases levels of protriptyline by unspecified interaction mechanism. Minor/Significance Unknown.

• pyridoxine

  sulfamethoxazole will decrease the level or effect of pyridoxine by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  trimethoprim will decrease the level or effect of pyridoxine by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

• pyridoxine (Antidote)

  sulfamethoxazole will decrease the level or effect of pyridoxine (Antidote) by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  trimethoprim will decrease the level or effect of pyridoxine (Antidote) by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

• pyrimethamine

  sulfamethoxazole, pyrimethamine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased bone marrow toxicity.

• quinine

  quinine will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• quinine

  sulfamethoxazole will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ramelteon

  sulfamethoxazole will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ribociclib

  ribociclib will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• rifampin

  rifampin will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• rifapentine

  rifapentine will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• salicylates (non-asa)

  salicylates (non-asa) increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• salsalate

  salsalate increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• secobarbital

  secobarbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• selegiline transdermal

  selegiline transdermal increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• spironolactone

  spironolactone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  spironolactone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  spironolactone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• sulfamethoxazole

  sulfamethoxazole will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulfasalazine

  sulfasalazine increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• thiamine

  sulfamethoxazole will decrease the level or effect of thiamine by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  trimethoprim will decrease the level or effect of thiamine by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

• ticlopidine

  ticlopidine will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• triamterene

  triamterene will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  triamterene, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.

• tolbutamide

  sulfamethoxazole will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• torsemide

  torsemide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• tranylcypromine

  tranylcypromine increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• trazodone

  sulfamethoxazole decreases levels of trazodone by unspecified interaction mechanism. Minor/Significance Unknown.

• triamterene

  sulfamethoxazole will increase the level or effect of triamterene by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  triamterene, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  triamterene increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• trimethoprim

  sulfamethoxazole will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trimipramine

  sulfamethoxazole decreases levels of trimipramine by unspecified interaction mechanism. Minor/Significance Unknown.

• valganciclovir

  valganciclovir increases toxicity of sulfamethoxazole by pharmacodynamic synergism. Minor/Significance Unknown.

• valproic acid

  valproic acid will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• verapamil

  sulfamethoxazole will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  trimethoprim will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• verteporfin

  sulfamethoxazole, verteporfin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased phototoxicity.

• voriconazole

  sulfamethoxazole will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  voriconazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• willow bark

  willow bark increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• zafirlukast

  zafirlukast will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• zidovudine

  zidovudine increases toxicity of sulfamethoxazole by pharmacodynamic synergism. Minor/Significance Unknown.
  
  sulfamethoxazole increases levels of zidovudine by decreasing renal clearance. Minor/Significance Unknown.

• abametapir

  Serious - Use Alternative (1)abametapir will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

• acetazolamide

  Minor (1)acetazolamide will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• aliskiren

  Monitor Closely (1)trimethoprim and aliskiren both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• alosetron

  Minor (1)sulfamethoxazole will increase the level or effect of alosetron by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• alpelisib

  Monitor Closely (1)alpelisib will decrease the level or effect of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• amantadine

  Monitor Closely (2)trimethoprim increases levels of amantadine by decreasing elimination. Use Caution/Monitor. Coadministration may impair renal clearance of amantadine, resulting in higher plasma concentrations.
  
  sulfamethoxazole increases levels of amantadine by decreasing elimination. Use Caution/Monitor. Coadministration may impair renal clearance of amantadine, resulting in higher plasma concentrations.

• amiloride

  Monitor Closely (1)trimethoprim and amiloride both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.Minor (3)amiloride, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  amiloride, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  amiloride increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• aminobenzoate potassium

  Serious - Use Alternative (1)aminobenzoate potassium decreases effects of sulfamethoxazole by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• aminohippurate sodium

  Minor (1)sulfamethoxazole, aminohippurate sodium. Other (see comment). Minor/Significance Unknown. Comment: This substance interferes with chemical color development of aminohippurate (PAH) essential to accurate renal clearance analysis.

• aminolevulinic acid oral

  Serious - Use Alternative (1)aminolevulinic acid oral, sulfamethoxazole. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

• aminolevulinic acid topical

  Serious - Use Alternative (1)sulfamethoxazole, aminolevulinic acid topical. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• amiodarone

  Monitor Closely (2)amiodarone will increase the level or effect of sulfamethoxazole by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  amiodarone will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (2)amiodarone and sulfamethoxazole both increase QTc interval. Avoid or Use Alternate Drug.
  
  amiodarone and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)amiodarone will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• amitriptyline

  Monitor Closely (2)amitriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown.

• amobarbital

  Minor (1)amobarbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• amoxapine

  Monitor Closely (2)amoxapine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amoxapine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of amoxapine by unspecified interaction mechanism. Minor/Significance Unknown.

• anastrozole

  Minor (1)anastrozole will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• antithrombin alfa

  Serious - Use Alternative (2)sulfamethoxazole increases effects of antithrombin alfa by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of antithrombin alfa by plasma protein binding competition. Avoid or Use Alternate Drug.

• antithrombin III

  Serious - Use Alternative (2)sulfamethoxazole increases effects of antithrombin III by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of antithrombin III by plasma protein binding competition. Avoid or Use Alternate Drug.

• apalutamide

  Monitor Closely (1)apalutamide will decrease the level or effect of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Coadministration of apalutamide, a weak CYP2C9 inducer, with drugs that are CYP2C9 substrates can result in lower exposure to these medications. Evaluate for loss of therapeutic effect if medication must be coadministered.Serious - Use Alternative (1)apalutamide will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• argatroban

  Serious - Use Alternative (2)sulfamethoxazole increases effects of argatroban by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of argatroban by plasma protein binding competition. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  Monitor Closely (2)sulfamethoxazole and artemether/lumefantrine both increase QTc interval. Modify Therapy/Monitor Closely.
  
  artemether/lumefantrine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• aspirin

  Monitor Closely (1)aspirin, sulfamethoxazole. Either increases effects of the other by plasma protein binding competition. Use Caution/Monitor. Due to high protein binding capacity of both drugs, one may displace the other when coadministered leading to an enhanced effect of the displaced drug; risk is low with low dose aspirin.

• aspirin rectal

  Minor (1)aspirin rectal increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• aspirin/citric acid/sodium bicarbonate

  Monitor Closely (1)aspirin/citric acid/sodium bicarbonate, sulfamethoxazole. Either increases effects of the other by plasma protein binding competition. Use Caution/Monitor. Due to high protein binding capacity of both drugs, one may displace the other when coadministered leading to an enhanced effect of the displaced drug; risk is low with low dose aspirin.Minor (1)aspirin/citric acid/sodium bicarbonate increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• azathioprine

  Minor (1)sulfamethoxazole, azathioprine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Leukopenia due to additive myelosuppression.

• azithromycin

  Minor (2)azithromycin and sulfamethoxazole both increase QTc interval. Minor/Significance Unknown.
  
  azithromycin and trimethoprim both increase QTc interval. Minor/Significance Unknown.

• balsalazide

  Minor (3)trimethoprim will decrease the level or effect of balsalazide by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  sulfamethoxazole will decrease the level or effect of balsalazide by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  balsalazide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• bazedoxifene/conjugated estrogens

  Monitor Closely (2)sulfamethoxazole will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  trimethoprim will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• BCG vaccine live

  Serious - Use Alternative (2)sulfamethoxazole decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.
  
  trimethoprim decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.

• bemiparin

  Serious - Use Alternative (2)sulfamethoxazole increases effects of bemiparin by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of bemiparin by plasma protein binding competition. Avoid or Use Alternate Drug.

• benazepril

  Monitor Closely (1)trimethoprim and benazepril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• bendroflumethiazide

  Minor (3)bendroflumethiazide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  bendroflumethiazide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  bendroflumethiazide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• biotin

  Minor (2)trimethoprim will decrease the level or effect of biotin by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  sulfamethoxazole will decrease the level or effect of biotin by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

• bivalirudin

  Serious - Use Alternative (2)sulfamethoxazole increases effects of bivalirudin by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of bivalirudin by plasma protein binding competition. Avoid or Use Alternate Drug.

• bosentan

  Minor (1)sulfamethoxazole will increase the level or effect of bosentan by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• bumetanide

  Minor (1)bumetanide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• butabarbital

  Minor (1)butabarbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• butalbital

  Minor (1)butalbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• canagliflozin

  Monitor Closely (1)trimethoprim and canagliflozin both increase serum potassium. Use Caution/Monitor.

• candesartan

  Monitor Closely (1)trimethoprim and candesartan both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• cannabidiol

  Monitor Closely (1)cannabidiol will increase the level or effect of trimethoprim by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C9 activity. Consider reducing the dose when concomitantly using CYP2C9 substrates.

• captopril

  Monitor Closely (1)trimethoprim and captopril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• carbamazepine

  Minor (1)carbamazepine will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• carvedilol

  Monitor Closely (1)sulfamethoxazole will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• celecoxib

  Minor (1)sulfamethoxazole will increase the level or effect of celecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• chlorothiazide

  Minor (3)chlorothiazide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  chlorothiazide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  chlorothiazide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• chlorpromazine

  Monitor Closely (2)chlorpromazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  chlorpromazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• chlorpropamide

  Monitor Closely (1)sulfamethoxazole increases levels of chlorpropamide by plasma protein binding competition. Use Caution/Monitor.

• chlorthalidone

  Minor (3)chlorthalidone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  chlorthalidone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  chlorthalidone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• cholera vaccine

  Serious - Use Alternative (1)trimethoprim, cholera vaccine. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid coadministration of cholera vaccine with systemic antibiotics since these agents may be active against the vaccine strain. Do not administer cholera vaccine to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination.

• choline magnesium trisalicylate

  Minor (1)choline magnesium trisalicylate increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• cimetidine

  Monitor Closely (2)cimetidine will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  cimetidine will increase the level or effect of sulfamethoxazole by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.Minor (1)cimetidine will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• clarithromycin

  Monitor Closely (2)clarithromycin and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  clarithromycin and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• clomipramine

  Monitor Closely (2)clomipramine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  clomipramine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of clomipramine by unspecified interaction mechanism. Minor/Significance Unknown.

• conjugated estrogens

  Monitor Closely (2)trimethoprim will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  sulfamethoxazole will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• crofelemer

  Monitor Closely (1)crofelemer increases levels of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• cyclopenthiazide

  Minor (3)cyclopenthiazide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  cyclopenthiazide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  cyclopenthiazide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Monitor Closely (2)trimethoprim and cyclosporine both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.
  
  sulfamethoxazole, cyclosporine. Either increases effects of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor.

• dabrafenib

  Monitor Closely (1)dabrafenib will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dalteparin

  Serious - Use Alternative (2)sulfamethoxazole increases effects of dalteparin by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of dalteparin by plasma protein binding competition. Avoid or Use Alternate Drug.

• dapsone

  Minor (2)sulfamethoxazole, dapsone. Either increases levels of the other by decreasing elimination. Minor/Significance Unknown.
  
  trimethoprim, dapsone. Either increases levels of the other by decreasing elimination. Minor/Significance Unknown.

• dapsone topical

  Monitor Closely (2)trimethoprim increases toxicity of dapsone topical by decreasing metabolism. Modify Therapy/Monitor Closely. Coadministration increases systemic exposure of dapsone and its metabolites (N-acetyl-dapsone, dapsone hydroxylamine). May induce methemoglobinemia.
  
  sulfamethoxazole increases toxicity of dapsone topical by decreasing metabolism. Modify Therapy/Monitor Closely. Coadministration increases systemic exposure of dapsone and its metabolites (N-acetyl-dapsone, dapsone hydroxylamine). May induce methemoglobinemia.

• desipramine

  Monitor Closely (2)desipramine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  desipramine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of desipramine by unspecified interaction mechanism. Minor/Significance Unknown.

• diclofenac

  Minor (1)sulfamethoxazole will increase the level or effect of diclofenac by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• diflunisal

  Minor (1)diflunisal increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• digoxin

  Monitor Closely (4)digoxin will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  sulfamethoxazole will increase the level or effect of digoxin by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  trimethoprim will increase the level or effect of digoxin by altering intestinal flora. Applies only to oral form of both agents. Use Caution/Monitor.
  
  sulfamethoxazole will increase the level or effect of digoxin by altering intestinal flora. Applies only to oral form of both agents. Use Caution/Monitor.

• diltiazem

  Minor (1)sulfamethoxazole will increase the level or effect of diltiazem by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• disopyramide

  Serious - Use Alternative (2)disopyramide and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.
  
  sulfamethoxazole and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.

• disulfiram

  Minor (1)disulfiram will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• dofetilide

  Monitor Closely (4)dofetilide and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole will increase the level or effect of dofetilide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  dofetilide will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  sulfamethoxazole and dofetilide both increase QTc interval. Modify Therapy/Monitor Closely.

• dolasetron

  Monitor Closely (2)sulfamethoxazole and dolasetron both increase QTc interval. Use Caution/Monitor.
  
  dolasetron and trimethoprim both increase QTc interval. Use Caution/Monitor.

• dosulepin

  Minor (1)sulfamethoxazole decreases levels of dosulepin by unspecified interaction mechanism. Minor/Significance Unknown.

• doxepin

  Monitor Closely (2)doxepin and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  doxepin and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of doxepin by unspecified interaction mechanism. Minor/Significance Unknown.

• dronabinol

  Monitor Closely (1)sulfamethoxazole will increase the level or effect of dronabinol by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Dronabinol is a CYP2C9 substrate.

• dronedarone

  Monitor Closely (2)sulfamethoxazole and dronedarone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  dronedarone and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• droperidol

  Monitor Closely (2)droperidol and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and droperidol both increase QTc interval. Modify Therapy/Monitor Closely.

• drospirenone

  Minor (3)drospirenone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  drospirenone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  drospirenone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.

• efavirenz

  Monitor Closely (1)efavirenz will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• elagolix

  Monitor Closely (1)elagolix decreases levels of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• eltrombopag

  Monitor Closely (1)sulfamethoxazole will increase the level or effect of eltrombopag by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• eluxadoline

  Monitor Closely (1)sulfamethoxazole increases levels of eluxadoline by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. As a precautionary measure due to incomplete information on the metabolism of eluxadoline, use caution when coadministered with strong CYP2C9/10 inhibitors.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (2)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF decreases levels of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Elvitegravir is a moderate CYP2C9 inducer.

• enalapril

  Monitor Closely (1)trimethoprim and enalapril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• encorafenib

  Monitor Closely (1)encorafenib, trimethoprim. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• enoxaparin

  Serious - Use Alternative (2)sulfamethoxazole increases effects of enoxaparin by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of enoxaparin by plasma protein binding competition. Avoid or Use Alternate Drug.

• epinephrine

  Monitor Closely (2)epinephrine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  epinephrine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• epinephrine racemic

  Monitor Closely (2)epinephrine racemic and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  epinephrine racemic and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• eplerenone

  Monitor Closely (1)trimethoprim and eplerenone both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• eprosartan

  Monitor Closely (1)trimethoprim and eprosartan both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• erdafitinib

  Monitor Closely (1)erdafitinib increases levels of trimethoprim by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.Serious - Use Alternative (2)trimethoprim will increase the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. If coadministration of a strong CYP2C9 inhibitors is unavoidable, closely monitor adverse reactions and modify dose of erdafitinib accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.
  
  sulfamethoxazole will increase the level or effect of erdafitinib by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with strong CYP2C9 inhibitors, monitor closely for adverse reactions and consider decreasing dose accordingly. If strong CYP2C9 inhibitor is discontinued, consider increasing erdafitinib dose in the absence of any drug-related toxicities.

• erythromycin base

  Monitor Closely (2)sulfamethoxazole and erythromycin base both increase QTc interval. Modify Therapy/Monitor Closely.
  
  erythromycin base and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• erythromycin ethylsuccinate

  Monitor Closely (2)erythromycin ethylsuccinate and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and erythromycin ethylsuccinate both increase QTc interval. Modify Therapy/Monitor Closely.

• erythromycin lactobionate

  Monitor Closely (2)erythromycin lactobionate and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and erythromycin lactobionate both increase QTc interval. Modify Therapy/Monitor Closely.

• erythromycin stearate

  Monitor Closely (2)sulfamethoxazole and erythromycin stearate both increase QTc interval. Modify Therapy/Monitor Closely.
  
  erythromycin stearate and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• estradiol

  Monitor Closely (2)trimethoprim will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  sulfamethoxazole will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• estrogens conjugated synthetic

  Monitor Closely (2)trimethoprim will decrease the level or effect of estrogens conjugated synthetic by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  sulfamethoxazole will decrease the level or effect of estrogens conjugated synthetic by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• estropipate

  Monitor Closely (2)trimethoprim will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  sulfamethoxazole will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• ethacrynic acid

  Minor (1)ethacrynic acid increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• ethinylestradiol

  Monitor Closely (2)trimethoprim will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  sulfamethoxazole will decrease the level or effect of ethinylestradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• ethotoin

  Monitor Closely (1)sulfamethoxazole will increase the level or effect of ethotoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)sulfamethoxazole increases levels of ethotoin by decreasing metabolism. Minor/Significance Unknown.

• etravirine

  Monitor Closely (1)sulfamethoxazole will increase the level or effect of etravirine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)etravirine will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• felbamate

  Minor (1)felbamate will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fexinidazole

  Serious - Use Alternative (1)fexinidazole will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• finerenone

  Monitor Closely (1)trimethoprim and finerenone both increase serum potassium. Modify Therapy/Monitor Closely. Finerenone dose adjustment based on current serum potassium concentration. Monitor serum potassium and adjust finerenone dose as described in the prescribing information as necessary.

• flecainide

  Monitor Closely (2)sulfamethoxazole and flecainide both increase QTc interval. Use Caution/Monitor.
  
  flecainide and trimethoprim both increase QTc interval. Use Caution/Monitor.

• fluconazole

  Monitor Closely (2)fluconazole and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and fluconazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)fluconazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluoxetine

  Monitor Closely (2)fluoxetine and trimethoprim both increase QTc interval. Use Caution/Monitor.
  
  fluoxetine will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• fluphenazine

  Monitor Closely (2)fluphenazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  fluphenazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• flurbiprofen

  Minor (1)sulfamethoxazole will increase the level or effect of flurbiprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluvastatin

  Minor (1)sulfamethoxazole will increase the level or effect of fluvastatin by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• fluvoxamine

  Monitor Closely (2)fluvoxamine and trimethoprim both increase QTc interval. Use Caution/Monitor.
  
  fluvoxamine and sulfamethoxazole both increase QTc interval. Use Caution/Monitor.

• folic acid

  Minor (1)sulfamethoxazole decreases levels of folic acid by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• fondaparinux

  Serious - Use Alternative (2)sulfamethoxazole increases effects of fondaparinux by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of fondaparinux by plasma protein binding competition. Avoid or Use Alternate Drug.

• formoterol

  Monitor Closely (2)sulfamethoxazole and formoterol both increase QTc interval. Modify Therapy/Monitor Closely.
  
  formoterol and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• foscarnet

  Monitor Closely (2)sulfamethoxazole and foscarnet both increase QTc interval. Use Caution/Monitor.
  
  foscarnet and trimethoprim both increase QTc interval. Use Caution/Monitor.

• fosinopril

  Monitor Closely (1)trimethoprim and fosinopril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• fosphenytoin

  Monitor Closely (2)sulfamethoxazole will increase the level or effect of fosphenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  fosphenytoin will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)sulfamethoxazole increases levels of fosphenytoin by decreasing metabolism. Minor/Significance Unknown.

• furosemide

  Minor (1)furosemide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• ganciclovir

  Minor (1)ganciclovir increases toxicity of sulfamethoxazole by pharmacodynamic synergism. Minor/Significance Unknown.

• glimepiride

  Monitor Closely (1)sulfamethoxazole increases levels of glimepiride by plasma protein binding competition. Use Caution/Monitor.

• glipizide

  Monitor Closely (1)sulfamethoxazole increases levels of glipizide by plasma protein binding competition. Use Caution/Monitor.

• glucarpidase

  Monitor Closely (2)glucarpidase will decrease the level or effect of sulfamethoxazole by increasing metabolism. Modify Therapy/Monitor Closely. Leucorvorin, reduced folates, and folate antimetabolites are substrates for glucarpidase (hydrolyzes glutamate residue from folic acid and antifolates)
  
  glucarpidase will decrease the level or effect of trimethoprim by increasing metabolism. Modify Therapy/Monitor Closely. Leucorvorin, reduced folates, and folate antimetabolites are substrates for glucarpidase (hydrolyzes glutamate residue from folic acid and antifolates)

• glyburide

  Monitor Closely (2)sulfamethoxazole increases levels of glyburide by plasma protein binding competition. Use Caution/Monitor.
  
  sulfamethoxazole increases levels of glyburide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Strong CYP2C9 inhibitors may decrease glyburide metabolism.

• haloperidol

  Monitor Closely (2)haloperidol and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and haloperidol both increase QTc interval. Modify Therapy/Monitor Closely.

• heparin

  Serious - Use Alternative (2)sulfamethoxazole increases effects of heparin by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of heparin by plasma protein binding competition. Avoid or Use Alternate Drug.

• hydrochlorothiazide

  Minor (5)hydrochlorothiazide will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  hydrochlorothiazide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  hydrochlorothiazide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  hydrochlorothiazide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  sulfamethoxazole will increase the level or effect of hydrochlorothiazide by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ibuprofen

  Minor (1)sulfamethoxazole will increase the level or effect of ibuprofen by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ibuprofen IV

  Minor (1)sulfamethoxazole will increase the level or effect of ibuprofen IV by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ibutilide

  Serious - Use Alternative (2)ibutilide and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.
  
  sulfamethoxazole and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.

• idelalisib

  Serious - Use Alternative (1)idelalisib will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

• iloperidone

  Monitor Closely (3)sulfamethoxazole and iloperidone both increase QTc interval. Use Caution/Monitor.
  
  iloperidone and trimethoprim both increase QTc interval. Use Caution/Monitor.
  
  iloperidone increases levels of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

• imatinib

  Monitor Closely (1)imatinib will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• imidapril

  Monitor Closely (1)sulfamethoxazole, imidapril. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

• imipramine

  Monitor Closely (2)imipramine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  imipramine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of imipramine by unspecified interaction mechanism. Minor/Significance Unknown.

• indapamide

  Serious - Use Alternative (2)sulfamethoxazole and indapamide both increase QTc interval. Avoid or Use Alternate Drug.
  
  indapamide and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.Minor (3)indapamide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  indapamide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  indapamide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• indinavir

  Monitor Closely (1)indinavir will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• indomethacin

  Minor (1)indomethacin increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• irbesartan

  Monitor Closely (1)trimethoprim and irbesartan both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• isavuconazonium sulfate

  Minor (1)isavuconazonium sulfate will increase the level or effect of trimethoprim by Other (see comment). Minor/Significance Unknown. Isavuconazonium sulfate, an OCT2 inhibitor, may increase the effects or levels of OCT2 substrates.

• isocarboxazid

  Minor (1)isocarboxazid increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• itraconazole

  Monitor Closely (2)sulfamethoxazole and itraconazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  itraconazole and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• ivosidenib

  Serious - Use Alternative (2)ivosidenib will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
  
  ivosidenib will decrease the level or effect of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2C9 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ketoconazole

  Monitor Closely (2)ketoconazole and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and ketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)ketoconazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• L-methylfolate

  Monitor Closely (1)trimethoprim decreases effects of L-methylfolate by Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Folic acid antagonists may interfere with folic acid utilization.Minor (1)sulfamethoxazole decreases levels of L-methylfolate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• lacosamide

  Monitor Closely (1)sulfamethoxazole increases levels of lacosamide by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Consider decreasing lacosamide dose when coadministered with strong CYP2C9 inhibitors.

• lamivudine

  Monitor Closely (1)trimethoprim increases effects of lamivudine by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor. Potential for increased toxicity.Minor (1)sulfamethoxazole increases levels of lamivudine by decreasing renal clearance. Minor/Significance Unknown.

• lapatinib

  Monitor Closely (1)sulfamethoxazole and lapatinib both increase QTc interval. Use Caution/Monitor.

• larotrectinib

  Minor (1)larotrectinib will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• leflunomide

  Minor (1)leflunomide will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• lenacapavir

  Monitor Closely (1)lenacapavir will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• lesinurad

  Monitor Closely (1)sulfamethoxazole will increase the level or effect of lesinurad by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely.

• leucovorin

  Serious - Use Alternative (1)leucovorin decreases effects of trimethoprim by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Monitor for trimethoprim treatment failure or decreased efficacy when coadministered with leucovorin, especially when used with sulfamethoxazole for Pneumocystis jiroveci pneumonia in patients who are HIV positive .

• levofloxacin

  Monitor Closely (2)sulfamethoxazole and levofloxacin both increase QTc interval. Use Caution/Monitor.
  
  levofloxacin and trimethoprim both increase QTc interval. Use Caution/Monitor.

• levoketoconazole

  Monitor Closely (2)levoketoconazole and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and levoketoconazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (2)levoketoconazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  levoketoconazole will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• levoleucovorin

  Serious - Use Alternative (1)levoleucovorin decreases effects of trimethoprim by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Monitor for trimethoprim treatment failure or decreased efficacy when coadministered with levoleucovorin, especially when used with sulfamethoxazole for Pneumocystis jiroveci pneumonia in patients who are HIV positive .

• levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

  Monitor Closely (2)trimethoprim will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.
  
  sulfamethoxazole will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor. Antibiotics may decrease hormonal contraceptive efficacy.

• linezolid

  Minor (1)linezolid increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• lisinopril

  Monitor Closely (1)trimethoprim and lisinopril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• lofepramine

  Monitor Closely (2)lofepramine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  lofepramine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of lofepramine by unspecified interaction mechanism. Minor/Significance Unknown.

• lonafarnib

  Serious - Use Alternative (1)lonafarnib will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

• lopinavir

  Serious - Use Alternative (1)lopinavir will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• losartan

  Monitor Closely (2)sulfamethoxazole will increase the level or effect of losartan by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. May inhibit the conversion of losartan to its active metabolite E-3174. Importance of interaction not established; monitor individual therapeutic response to determine losartan dosage.
  
  trimethoprim and losartan both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.Minor (1)sulfamethoxazole decreases effects of losartan by decreasing metabolism. Minor/Significance Unknown. May inhibit the conversion of losartan to its active metabolite E-3174. Importance of interaction not established; monitor individual therapeutic response to determine losartan dosage.

• lumacaftor/ivacaftor

  Monitor Closely (1)lumacaftor/ivacaftor, trimethoprim. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. In vitro studies suggest that lumacaftor may induce and ivacaftor may inhibit CYP2C9 substrates. .

• lumefantrine

  Monitor Closely (2)lumefantrine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and lumefantrine both increase QTc interval. Modify Therapy/Monitor Closely.

• maprotiline

  Monitor Closely (2)maprotiline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  maprotiline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of maprotiline by unspecified interaction mechanism. Minor/Significance Unknown.

• mefloquine

  Serious - Use Alternative (2)mefloquine increases toxicity of trimethoprim by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.
  
  mefloquine increases toxicity of sulfamethoxazole by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.

• meloxicam

  Minor (1)sulfamethoxazole will increase the level or effect of meloxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• memantine

  Minor (2)memantine will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  sulfamethoxazole will increase the level or effect of memantine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mesalamine

  Minor (1)mesalamine increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• mestranol

  Monitor Closely (2)trimethoprim will decrease the level or effect of mestranol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
  
  sulfamethoxazole will decrease the level or effect of mestranol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.

• metformin

  Monitor Closely (1)trimethoprim increases levels of metformin by Other (see comment). Use Caution/Monitor. Comment: Trimethoprim may inhibit active renal tubular secretion of metformin (eg, via OCT2, MATE1); dose adjustments may be necessary.Minor (2)sulfamethoxazole will increase the level or effect of metformin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  metformin will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methadone

  Monitor Closely (2)sulfamethoxazole and methadone both increase QTc interval. Use Caution/Monitor.
  
  methadone and trimethoprim both increase QTc interval. Use Caution/Monitor.

• methenamine

  Serious - Use Alternative (1)methenamine, sulfamethoxazole. Other (see comment). Contraindicated. Comment: This combination may form an insoluble precipitate in the urine, decreasing the effects of both agents.

• methotrexate

  Monitor Closely (1)trimethoprim increases toxicity of methotrexate by Other (see comment). Use Caution/Monitor. Comment: Trimethoprim may increase risk of methotrexate-induced bone marrow suppression and megaloblastic anemia. If this drug combination cannot be avoided, closely monitor for signs of hematologic toxicity.Serious - Use Alternative (2)sulfamethoxazole increases toxicity of methotrexate by plasma protein binding competition. Avoid or Use Alternate Drug. Methotrexate concentrations may be elevated, increasing the risk of toxicity (eg, bone marrow suppression).
  
  trimethoprim, methotrexate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Due to an additive antifolate effect, trimethoprim has been shown to rarely increase bone marrow suppression in patients receiving methotrexate.

• methoxsalen

  Monitor Closely (1)methoxsalen, sulfamethoxazole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

• methyclothiazide

  Minor (4)methyclothiazide, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  methyclothiazide will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  methyclothiazide, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  sulfamethoxazole will increase the level or effect of methyclothiazide by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methyl aminolevulinate

  Serious - Use Alternative (1)sulfamethoxazole, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• metolazone

  Minor (3)metolazone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  metolazone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.
  
  metolazone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• metronidazole

  Monitor Closely (1)metronidazole, sulfamethoxazole. Mechanism: decreasing metabolism. Use Caution/Monitor. Disulfiram like reaction.Minor (1)metronidazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• miconazole vaginal

  Minor (1)miconazole vaginal will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• microbiota oral

  Serious - Use Alternative (1)trimethoprim decreases effects of microbiota oral by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Microbiota oral contains bacterial spores. Antibacterial agents may decrease efficacy if coadministered. Complete antibiotic regimens 2-4 days before initiating microbiota oral. .

• midodrine

  Minor (2)sulfamethoxazole will increase the level or effect of midodrine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  midodrine will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mineral oil

  Minor (1)mineral oil decreases levels of sulfamethoxazole by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• mipomersen

  Monitor Closely (1)mipomersen, sulfamethoxazole. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• mitotane

  Monitor Closely (1)mitotane decreases levels of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

• moexipril

  Monitor Closely (1)trimethoprim and moexipril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• moxifloxacin

  Monitor Closely (2)sulfamethoxazole and moxifloxacin both increase QTc interval. Modify Therapy/Monitor Closely.
  
  moxifloxacin and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• nateglinide

  Monitor Closely (2)sulfamethoxazole will increase the level or effect of nateglinide by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  sulfamethoxazole increases levels of nateglinide by plasma protein binding competition. Use Caution/Monitor.Minor (1)nateglinide will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• nilotinib

  Monitor Closely (1)sulfamethoxazole and nilotinib both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)nilotinib will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• nitazoxanide

  Minor (1)nitazoxanide, sulfamethoxazole. Either increases levels of the other by Mechanism: plasma protein binding competition. Minor/Significance Unknown.

• nitisinone

  Monitor Closely (1)nitisinone will increase the level or effect of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Nitisinone inhibits CYP2C9. Caution if CYP2C9 substrate coadministered, particularly those with a narrow therapeutic index.

• nortriptyline

  Monitor Closely (2)nortriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  nortriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of nortriptyline by unspecified interaction mechanism. Minor/Significance Unknown.

• octreotide

  Monitor Closely (2)octreotide and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and octreotide both increase QTc interval. Modify Therapy/Monitor Closely.

• octreotide (Antidote)

  Monitor Closely (2)octreotide (Antidote) and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  sulfamethoxazole and octreotide (Antidote) both increase QTc interval. Modify Therapy/Monitor Closely.

• ofloxacin

  Monitor Closely (2)sulfamethoxazole and ofloxacin both increase QTc interval. Use Caution/Monitor.
  
  ofloxacin and trimethoprim both increase QTc interval. Use Caution/Monitor.Minor (2)ofloxacin will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  sulfamethoxazole will increase the level or effect of ofloxacin by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• olmesartan

  Monitor Closely (1)trimethoprim and olmesartan both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• omeprazole

  Minor (1)omeprazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ospemifene

  Monitor Closely (2)sulfamethoxazole increases levels of ospemifene by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.
  
  sulfamethoxazole, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

• paclitaxel

  Monitor Closely (1)trimethoprim will increase the level or effect of paclitaxel by Other (see comment). Use Caution/Monitor. Paclitaxel levels/toxicity may increase when coadministered with CYP2C8 inhibitors

• paclitaxel protein bound

  Monitor Closely (1)trimethoprim will increase the level or effect of paclitaxel protein bound by Other (see comment). Use Caution/Monitor. Paclitaxel levels/toxicity may increase when coadministered with CYP2C8 inhibitors

• paliperidone

  Monitor Closely (2)sulfamethoxazole and paliperidone both increase QTc interval. Use Caution/Monitor.
  
  paliperidone and trimethoprim both increase QTc interval. Use Caution/Monitor.

• pantothenic acid

  Minor (2)trimethoprim will decrease the level or effect of pantothenic acid by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  sulfamethoxazole will decrease the level or effect of pantothenic acid by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

• parecoxib

  Monitor Closely (1)sulfamethoxazole will increase the level or effect of parecoxib by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• paroxetine

  Monitor Closely (2)paroxetine and trimethoprim both increase QTc interval. Use Caution/Monitor.
  
  sulfamethoxazole and paroxetine both increase QTc interval. Use Caution/Monitor.

• patiromer

  Minor (1)patiromer, trimethoprim. cation binding in GI tract. Minor/Significance Unknown. No observed clinically important interaction. No separation of dosing required.

• pazopanib

  Minor (1)sulfamethoxazole and pazopanib both increase QTc interval. Minor/Significance Unknown.

• pentamidine

  Monitor Closely (1)trimethoprim and pentamidine both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.Serious - Use Alternative (2)sulfamethoxazole and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.
  
  pentamidine and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.

• pentobarbital

  Minor (1)pentobarbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• perindopril

  Monitor Closely (1)trimethoprim and perindopril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• perphenazine

  Monitor Closely (2)perphenazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• pexidartinib

  Serious - Use Alternative (1)sulfamethoxazole and pexidartinib both increase inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Pexidartinib can cause hepatotoxicity. Avoid coadministration of pexidartinib with other products know to cause hepatoxicity.

• phenelzine

  Minor (1)phenelzine increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• phenindione

  Serious - Use Alternative (2)sulfamethoxazole increases effects of phenindione by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of phenindione by plasma protein binding competition. Avoid or Use Alternate Drug.

• phenobarbital

  Minor (1)phenobarbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• phenytoin

  Monitor Closely (1)sulfamethoxazole will increase the level or effect of phenytoin by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.Minor (1)sulfamethoxazole increases levels of phenytoin by decreasing metabolism. Minor/Significance Unknown.

• pimozide

  Serious - Use Alternative (2)sulfamethoxazole and pimozide both increase QTc interval. Avoid or Use Alternate Drug.
  
  pimozide and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)sulfamethoxazole decreases levels of pimozide by unspecified interaction mechanism. Minor/Significance Unknown.

• piroxicam

  Minor (1)sulfamethoxazole will increase the level or effect of piroxicam by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• porfimer

  Monitor Closely (1)sulfamethoxazole, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

• posaconazole

  Monitor Closely (2)sulfamethoxazole and posaconazole both increase QTc interval. Use Caution/Monitor.
  
  posaconazole and trimethoprim both increase QTc interval. Use Caution/Monitor.

• potassium acid phosphate

  Monitor Closely (1)trimethoprim and potassium acid phosphate both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• potassium chloride

  Monitor Closely (1)trimethoprim and potassium chloride both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• potassium citrate

  Monitor Closely (1)trimethoprim and potassium citrate both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• potassium citrate/citric acid

  Monitor Closely (1)trimethoprim and potassium citrate/citric acid both increase serum potassium. Use Caution/Monitor.

• pralatrexate

  Monitor Closely (1)sulfamethoxazole increases levels of pralatrexate by decreasing renal clearance. Use Caution/Monitor.

• pretomanid

  Serious - Use Alternative (1)sulfamethoxazole, pretomanid. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Pretomanid regimen associated with hepatotoxicity. Avoid alcohol and hepatotoxic agents, including herbal supplements and drugs other than bedaquiline and linezolid.

• primaquine

  Minor (1)primaquine, sulfamethoxazole. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hemolysis in G6PD deficient pts.

• primidone

  Minor (1)primidone will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• probenecid

  Minor (1)probenecid increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• procainamide

  Monitor Closely (2)sulfamethoxazole will increase the level or effect of procainamide by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  procainamide will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (2)sulfamethoxazole and procainamide both increase QTc interval. Avoid or Use Alternate Drug.
  
  procainamide and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.

• prochlorperazine

  Monitor Closely (2)prochlorperazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  prochlorperazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• promazine

  Monitor Closely (3)promazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  promazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  promazine increases toxicity of sulfamethoxazole by unspecified interaction mechanism. Use Caution/Monitor. Enhanced myelosuppression.

• promethazine

  Monitor Closely (2)promethazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  promethazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• protamine

  Serious - Use Alternative (2)sulfamethoxazole increases effects of protamine by decreasing metabolism. Avoid or Use Alternate Drug.
  
  sulfamethoxazole increases effects of protamine by plasma protein binding competition. Avoid or Use Alternate Drug.

• protriptyline

  Monitor Closely (2)protriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  protriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of protriptyline by unspecified interaction mechanism. Minor/Significance Unknown.

• pyridoxine

  Minor (2)trimethoprim will decrease the level or effect of pyridoxine by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  sulfamethoxazole will decrease the level or effect of pyridoxine by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

• pyridoxine (Antidote)

  Minor (2)sulfamethoxazole will decrease the level or effect of pyridoxine (Antidote) by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  trimethoprim will decrease the level or effect of pyridoxine (Antidote) by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

• pyrimethamine

  Minor (1)sulfamethoxazole, pyrimethamine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased bone marrow toxicity.

• quinapril

  Monitor Closely (1)trimethoprim and quinapril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• quinidine

  Monitor Closely (2)quinidine will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  quinidine will increase the level or effect of sulfamethoxazole by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.Serious - Use Alternative (2)quinidine and sulfamethoxazole both increase QTc interval. Avoid or Use Alternate Drug.
  
  quinidine and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.

• quinine

  Minor (2)sulfamethoxazole will increase the level or effect of quinine by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  quinine will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ramelteon

  Minor (1)sulfamethoxazole will increase the level or effect of ramelteon by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• ramipril

  Monitor Closely (1)trimethoprim and ramipril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• ranolazine

  Monitor Closely (2)sulfamethoxazole and ranolazine both increase QTc interval. Use Caution/Monitor.
  
  ranolazine and trimethoprim both increase QTc interval. Use Caution/Monitor.

• repaglinide

  Monitor Closely (2)trimethoprim increases levels of repaglinide by decreasing metabolism. Use Caution/Monitor. Hepatic cytochrome P450 2C8.
  
  sulfamethoxazole increases levels of repaglinide by plasma protein binding competition. Use Caution/Monitor.

• ribociclib

  Minor (1)ribociclib will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• rifabutin

  Monitor Closely (1)rifabutin will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifampin

  Monitor Closely (1)rifampin will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)rifampin will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• rifapentine

  Minor (1)rifapentine will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• risperidone

  Monitor Closely (2)risperidone and trimethoprim both increase QTc interval. Use Caution/Monitor.
  
  sulfamethoxazole and risperidone both increase QTc interval. Use Caution/Monitor.

• sacubitril/valsartan

  Monitor Closely (1)sacubitril/valsartan and trimethoprim both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• salicylates (non-asa)

  Minor (1)salicylates (non-asa) increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• salsalate

  Minor (1)salsalate increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• secobarbital

  Minor (1)secobarbital will decrease the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• selegiline transdermal

  Minor (1)selegiline transdermal increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• selexipag

  Monitor Closely (1)trimethoprim will increase the level or effect of selexipag by decreasing metabolism. Modify Therapy/Monitor Closely. Reduce selexipag dose to once daily if coadministered with moderate CYP2C8 inhibitors.

• siponimod

  Serious - Use Alternative (2)trimethoprim will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.
  
  sulfamethoxazole will increase the level or effect of siponimod by affecting hepatic enzyme CYP2C9/10 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with drugs that cause moderate CYP2C9 AND a moderate or strong CYP3A4 inhibition is not recommended. Caution if siponimod coadministered with moderate CYP2C9 inhibitors alone.

• sodium picosulfate/magnesium oxide/anhydrous citric acid

  Monitor Closely (2)trimethoprim decreases effects of sodium picosulfate/magnesium oxide/anhydrous citric acid by altering metabolism. Use Caution/Monitor. Coadministration with antibiotics decreases efficacy by altering colonic bacterial flora needed to convert sodium picosulfate to active drug.
  
  sulfamethoxazole decreases effects of sodium picosulfate/magnesium oxide/anhydrous citric acid by altering metabolism. Use Caution/Monitor. Coadministration with antibiotics decreases efficacy by altering colonic bacterial flora needed to convert sodium picosulfate to active drug.

• sotalol

  Serious - Use Alternative (2)sulfamethoxazole and sotalol both increase QTc interval. Avoid or Use Alternate Drug.
  
  sotalol and trimethoprim both increase QTc interval. Avoid or Use Alternate Drug.

• sparsentan

  Monitor Closely (1)sparsentan will decrease the level or effect of trimethoprim by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C9 inducer) decreases exposure of CYP2C9 substrates and reduces efficacy related to these substrates.

• spironolactone

  Monitor Closely (1)trimethoprim and spironolactone both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.Minor (3)spironolactone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  spironolactone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  spironolactone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• sulfamethoxazole

  Monitor Closely (1)sulfamethoxazole and trimethoprim both increase QTc interval. Use Caution/Monitor.Minor (1)sulfamethoxazole will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulfasalazine

  Minor (1)sulfasalazine increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• tafenoquine

  Serious - Use Alternative (1)tafenoquine will increase the level or effect of trimethoprim by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.

• tamoxifen

  Monitor Closely (1)sulfamethoxazole, tamoxifen. affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor. CYP2C9/10 inhibition decreases tamoxifen metabolism to active metabolites.

• tecovirimat

  Monitor Closely (1)tecovirimat will decrease the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• telavancin

  Monitor Closely (2)telavancin and trimethoprim both increase QTc interval. Use Caution/Monitor.
  
  sulfamethoxazole and telavancin both increase QTc interval. Use Caution/Monitor.

• telmisartan

  Monitor Closely (1)trimethoprim and telmisartan both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• terbinafine

  Monitor Closely (1)sulfamethoxazole will increase the level or effect of terbinafine by affecting hepatic enzyme CYP2C9/10 metabolism. Use Caution/Monitor.

• thiamine

  Minor (2)trimethoprim will decrease the level or effect of thiamine by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
  
  sulfamethoxazole will decrease the level or effect of thiamine by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.

• thioridazine

  Monitor Closely (2)thioridazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  thioridazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• ticlopidine

  Minor (1)ticlopidine will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• tolazamide

  Monitor Closely (1)sulfamethoxazole increases levels of tolazamide by plasma protein binding competition. Use Caution/Monitor.

• tolbutamide

  Monitor Closely (1)sulfamethoxazole increases levels of tolbutamide by plasma protein binding competition. Use Caution/Monitor.Minor (1)sulfamethoxazole will increase the level or effect of tolbutamide by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• torsemide

  Minor (1)torsemide increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• trandolapril

  Monitor Closely (1)trimethoprim and trandolapril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• tranylcypromine

  Minor (1)tranylcypromine increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• trazodone

  Monitor Closely (2)trazodone and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  trazodone and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of trazodone by unspecified interaction mechanism. Minor/Significance Unknown.

• tretinoin

  Serious - Use Alternative (1)sulfamethoxazole, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• tretinoin topical

  Serious - Use Alternative (1)sulfamethoxazole, tretinoin topical. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• triamterene

  Monitor Closely (1)trimethoprim and triamterene both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.Minor (5)triamterene, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  sulfamethoxazole will increase the level or effect of triamterene by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  triamterene, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Hyperkalemia.
  
  triamterene increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  triamterene will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trifluoperazine

  Monitor Closely (2)trifluoperazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  trifluoperazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• trilaciclib

  Serious - Use Alternative (1)trilaciclib will decrease the level or effect of trimethoprim by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.

• trimethoprim

  Monitor Closely (1)sulfamethoxazole and trimethoprim both increase QTc interval. Use Caution/Monitor.Minor (1)sulfamethoxazole will increase the level or effect of trimethoprim by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• trimipramine

  Monitor Closely (2)trimipramine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  trimipramine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of trimipramine by unspecified interaction mechanism. Minor/Significance Unknown.

• tropisetron

  Monitor Closely (2)trimethoprim and tropisetron both increase QTc interval. Use Caution/Monitor.
  
  sulfamethoxazole and tropisetron both increase QTc interval. Use Caution/Monitor.

• tucatinib

  Serious - Use Alternative (2)trimethoprim will increase the level or effect of tucatinib by Other (see comment). Avoid or Use Alternate Drug. Coadministration of tucatinib (a CYP2C8 substrate) with a strong or moderate CYP2C8 inhibitors increases tucatinib plasma concentrations and risk of toxicities.
  
  tucatinib will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• typhoid vaccine live

  Serious - Use Alternative (2)sulfamethoxazole decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.
  
  trimethoprim decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.

• valganciclovir

  Minor (1)valganciclovir increases toxicity of sulfamethoxazole by pharmacodynamic synergism. Minor/Significance Unknown.

• valproic acid

  Minor (1)valproic acid will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• valsartan

  Monitor Closely (1)valsartan and trimethoprim both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

• venlafaxine

  Monitor Closely (2)sulfamethoxazole and venlafaxine both increase QTc interval. Use Caution/Monitor.
  
  trimethoprim and venlafaxine both increase QTc interval. Use Caution/Monitor.

• verapamil

  Minor (2)sulfamethoxazole will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  trimethoprim will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• verteporfin

  Minor (1)sulfamethoxazole, verteporfin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased phototoxicity.

• voclosporin

  Monitor Closely (1)voclosporin and trimethoprim both decrease serum potassium. Use Caution/Monitor.

• voriconazole

  Monitor Closely (2)trimethoprim and voriconazole both increase QTc interval. Use Caution/Monitor.
  
  sulfamethoxazole and voriconazole both increase QTc interval. Use Caution/Monitor.Minor (2)sulfamethoxazole will increase the level or effect of voriconazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.
  
  voriconazole will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of trimethoprim by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

• warfarin

  Monitor Closely (1)sulfamethoxazole will increase the level or effect of warfarin by affecting hepatic enzyme CYP2C9/10 metabolism. Modify Therapy/Monitor Closely. Mechanism of interaction may be caused by CYP2C9 inhibition and protein-binding displacement. If coadministered, consider decreasing warfarin dose by 10-20%.

• willow bark

  Minor (1)willow bark increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• zafirlukast

  Minor (1)zafirlukast will increase the level or effect of sulfamethoxazole by affecting hepatic enzyme CYP2C9/10 metabolism. Minor/Significance Unknown.

• zidovudine

  Monitor Closely (1)trimethoprim increases levels of zidovudine by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .Minor (2)sulfamethoxazole increases levels of zidovudine by decreasing renal clearance. Minor/Significance Unknown.
  
  zidovudine increases toxicity of sulfamethoxazole by pharmacodynamic synergism. Minor/Significance Unknown.

• ziprasidone

  Monitor Closely (2)sulfamethoxazole and ziprasidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  trimethoprim and ziprasidone both increase QTc interval. Modify Therapy/Monitor Closely.