trimethoprim/sulfamethoxazole (Rx)

Brand and Other Names:Bactrim, Bactrim DS, more...Septra, Septra DS, Cotrim, cotrimoxazole, Sulfatrim
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

trimethoprim/sulfamethoxazole

injected solution

  • (16mg/80mg)/mL

oral suspension

  • (40mg/200mg)/5mL

tablet

  • 80mg/400mg
  • 160mg/800mg

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

Dosage Forms & Strengths

trimethoprim/sulfamethoxazole

injected solution

  • (16mg/80mg)/mL

oral solution

  • (40mg/200mg)/5mL

tablet

  • 80mg/400mg
  • 160mg/800mg

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  

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Interactions

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              • 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.

              • 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.

              • 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.

              • warfarin

                sulfamethoxazole increases effects of warfarin by decreasing metabolism. Avoid or Use Alternate Drug.

                sulfamethoxazole increases effects of warfarin by plasma protein binding competition. Avoid or Use Alternate Drug.

              Monitor Closely (190)

              • 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.

              • dasatinib

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

              • desipramine

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

              • desipramine

                desipramine and sulfamethoxazole 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.

                sulfamethoxazole will increase the level or effect of digoxin by altering intestinal flora. Applies only to oral form of both agents. 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.

              • 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.

              • 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.

              • 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.

              • 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.

              • tamoxifen

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

              • 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.

              • 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. Use Caution/Monitor.

              • 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 (131)

              • 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.

              • azithromycin

                azithromycin and trimethoprim both increase QTc interval. 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.

              • balsalazide

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

                trimethoprim 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.

              • 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.

              • 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.

              • leflunomide

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

              • linezolid

                linezolid increases levels of sulfamethoxazole by unspecified interaction mechanism. 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

                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

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

              • metformin

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

              • 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.

              • 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.

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              Adverse Effects

              Frequency Not Defined

              Anorexia

              Nausea

              Vomiting

              Vertigo

              Seizure

              Peripheral neuritis

              Erythema multiforme

              Hyperkalemia

              Rash

              Urticaria

              Immune hypersensitivity reaction

              Stevens-Johnson syndrome

              Toxic epidermal necrolysis

              Agranulocytosis

              Aplastic anemia

              Hyponatremia

              Disorder of hematopoietic structure

              Fulminant hepatic necrosis

              Postmarketing Reports

              Thrombotic thrombocytopenia purpura

              Idiopathic thrombocytopenic purpura

              QT prolongation resulting in ventricular tachycardia and torsade de pointes

              Embryo-fetal toxicity

              Hypersensitivity and other fatal reactions

              Thrombocytopenia

              Clostridium difficile-associated diarrhea

              Sulfite sensitivity

              Risk associated with concurrent use of leucovorin for

              Pneumocystis jirovecii

              Pneumonia

              Infusion reactions

              Hypoglycemia

              Electrolyte abnormalities

              Thrombophlebitis

              Propylene glycol Toxicity

              Metabolic acidosis

              Drug reaction with eosinophilia and systemic symptoms (DRESS)

              Acute generalized exanthematous pustulosis (AGEP)

              Acute febrile neutrophilic dermatosis (AFND)

              Circulatory shock

              Acute and delayed lung injury

              Interstitial lung disease

              Acute respiratory failure

              Renal failure, interstitial nephritis, BUN and serum creatinine elevation, renal insufficiency, oliguria and anuria, crystalluria, and nephrotoxicity in association with cyclosporine

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              Warnings

              Contraindications

              Known hypersensitivity

              Age <2 months

              CrCl <15 mL/min when renal function status cannot be monitored

              Documented megaloblastic or folate deficiency anemia

              Significan hepatic impairment

              Contraindicated in pregnant patients at term and in nursing mothers, because sulfonamides, which pass the placenta and are excreted in the milk, may cause kernicterus

              History of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides

              Concomitant administration with dofetilide

              Cautions

              Not for use in areas with resistance rates >10%

              Severe and symptomatic hyponatremia can occur in patients receiving sulfamethoxazole/ trimethoprim, particularly for treatment of P. jirovecii pneumonia; evaluation for hyponatremia and appropriate correction is necessary in symptomatic patients to prevent life-threatening complications

              If patient treated for Pneumocystis jirovecii develops skin rash, fever, leukopenia, or any other sign of adverse reaction, therapy or re-challenge should be re-evaluated

              Circulatory shock with fever, severe hypotension, and confusion requiring intravenous fluid resuscitation and vasopressors has occurred within minutes to hours of re-challenge with trimethoprim-sulfamethoxazole in patients with history of recent (days to weeks) exposure to sulfamethoxazole-trimethoprim

              Fatalities associated with the administration of sulfonamides, although rare, have occurred due to severe reactions, including severe cutaneous adverse reactions (SCARs), including Stevens-Johnson Syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP) and acute febrile neutrophilic dermatosis (AFND), fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias; clinical signs, such as rash, sore throat, fever, arthralgia, pallor, purpura or jaundice may be early indications of serious reactions; discontinue therapy at first appearance of skin rash or any sign of serious adverse reaction

              Acute and delayed lung injury; anaphylaxis and circulatory shock have occurred with administration of sulfamethoxazole and trimethoprim products

              Cough, shortness of breath and pulmonary infiltrates potentially representing hypersensitivity reactions of the respiratory tract reported in association with sulfamethoxazole and trimethoprim treatment

              Severe pulmonary adverse reactions occurring within days to week of initiation of treatment and resulting in prolonged respiratory failure requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO), lung transplantation or death also reported in patients and otherwise healthy individuals treated with sulfamethoxazole and trimethoprim products

              Caution when used in elderly individuals; risk of bone marrow suppression

              PCP prophylaxis with AIDS: Rash, fever, leukopenia, and elevated transaminase values reported; hyperkalemia and hyponatremia also appear to be increased

              Severe cases (including fatalities) of immune-mediated thrombocytopenia reported; monitor patients for hematologic toxicity; resolves within a week upon discontinuation of therapy

              Sulfonamides should not be used to treat group A beta-hemolytic streptococcal infections; they will not eradicate streptococcus or prevent rheumatic fever

              Clostridium difficile-associated diarrhea reported

              Coadministration with leucovorin for the treatment of HIV-positive patients with PCP resulted in treatment failure and excess mortality in a randomized, placebo-controlled trial; avoid coadministration

              Development of drug-resistant bacteria may occur when prescribed in absence of strongly suspected bacterial infection or prophylactic indication

              Prolonged use may result in fungal or bacterial superinfection

              Caution with impaired renal or hepatic function, patients with possible folate deficiency (eg, the elderly, chronic alcoholics, patients receiving anticonvulsant therapy, patients with malabsorption syndrome, and patients in malnutrition states), and patients with severe allergies or bronchial asthma

              Hematological changes indicative of folic acid deficiency may occur in elderly patients or in patients with preexisting folic acid deficiency or kidney failure; effects are reversible by folinic acid therapy

              Hemolysis may occur if administered to patients with G6PD deficiency

              Hypoglycemia (rare) reported in nondiabetic patients; patients with renal dysfunction, liver disease, or malnutrition or those receiving high doses at particular risk

              Trimethoprim may impair phenylalanine metabolism but may have no significance in phenylketonuric patients on appropriate dietary restriction

              Caution with porphyria or thyroid dysfunction; sulfonamides can precipitate porphyria crisis and hypothyroidism; avoid use in patients with porphyria or thyroid dysfunction

              Complete blood counts should be done frequently in patients receiving therapy; discontinue therapy if a significant reduction in count of any formed blood element is noted’ perform urinalyses with careful microscopic examination and renal function tests during therapy, particularly for those patients with impaired renal function

              When administered at high doses as for the treatment of P. jirovecii pneumonia, monitor for total daily intake of propylene glycol from all sources and for acid-base disturbances; discontinue therapy if propylene glycol toxicity suspected

              Treatment failure and excess mortality were observed when trimethoprim-sulfamethoxazole was used concomitantly with leucovorin for treatment of HIV positive patients with Pneumocystis jirovecii pneumonia; co-administration of trimethoprim-sulfamethoxazole and leucovorin during treatment of Pneumocystis jirovecii pneumonia should be avoided

              During treatment, adequate fluid intake and urinary output should be ensured to prevent crystalluria; patients who are “slow acetylators” may be more prone to idiosyncratic reactions to sulfonamides

              Hyperkalemia

              • High dosage of trimethoprim, as used in patients with P. jirovecii pneumonia, induces a progressive but reversible increase of serum potassium concentrations in a substantial number of patients
              • Treatment with recommended doses may cause hyperkalemia when trimethoprim is administered to patients with underlying disorders of potassium metabolism, with renal insufficiency, or if drugs known to induce hyperkalemia are given concomitantly; close monitoring of serum potassium recommended

              Risk in treatment of Pneumocystis jirovecy pneumonia

              • AIDS patients may not tolerate or respond to sulfamethoxazole/ trimethoprim in same manner as non-AIDS patients
              • Incidence of adverse reactions, particularly rash, fever, leukopenia and elevated aminotransferase (transaminase) values, with therapy in AIDS patients who are being treated for P. jirovecii pneumonia reported to be increased compared with incidence normally associated with use of drug in non-AIDS patients
              • If a patient develops skin rash, fever, leukopenia or any sign of adverse reaction, reevaluate benefit-risk of continuing therapy or re-challenge with drug
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              Pregnancy & Lactation

              Pregnancy

              Therapy may cause fetal harm if administered to pregnant woman; some epidemiologic studies suggest that exposure to drug during pregnancy may be associated with increased risk of congenital malformations, particularly neural tube defects, cardiovascular abnormalities, urinary tract defects, oral clefts, and club foot

              Urinary tract infection in pregnancy is associated with adverse perinatal outcomes such as preterm birth, low birth weight, and pre-eclampsia, and increased mortality to pregnant woman

              P. jirovecii pneumonia in pregnancy is associated with preterm birth and increased morbidity and mortality for the pregnant woman

              Use during pregnancy only if potential benefit justifies potential risk to fetus

              Lactation

              Levels of drug in breast milk are approximately 2 to 5% of recommended daily dose for pediatric patients over two months of age; there is no information regarding effect of therapy on breastfed infant or effect on milk production; because of potential risk of bilirubin displacement and kernicterus on breastfed child, advise women to avoid breastfeeding during therapy

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Blocks 2 consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria

              Trimethoprim: Inhibits dihydrofolate reductase, thereby blocking production of tetrahydrofolic acid from dihydrofolic acid

              Sulfamethoxazole: Inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid

              Absorption

              Time to peak: 1-4 hours

              Distribution

              Protein bound: TMP (44%); SMX (70%)

              Metabolism

              Hepatic

              Enzymes inhibited: Hepatic CYP2C9

              Elimination

              Half-life: TMP (8-10 hr); SMX (10 hr)

              Excretion: Urine (as unchanged drug)

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              Administration

              IV Incompatibilities

              Additive: Fluconazole, linezolid, verapamil

              Y-site: Cisatracurium (incompatible at 2 mg/mL cisatra; may be compatible at much lower concs), fluconazole, foscarnet (may be compatible at very low TMP/SMX concs), midazolam, vinorelbine

              IV Preparation

              Do not use NS as diluent

              Injection vehicle contains benzyl alcohol and sodium metabisulfite

              Stability of parenteral admixture at room temperature (25°C)

              • 5 mL/125 mL D5W: 6 hr
              • 5 mL/100 mL D5W: 4 hr
              • 5 mL/75 mL D5W: 2 hr

              IV Administration

              Infuse over 60-90 min; give q6hr, 8hr, or 12hr

              Must be diluted well

              May be given less diluted in a central line

              Not for IM

              Maintain adequate fluid intake to prevent crystalluria

              Storage

              Do not refrigerate injection

              Less soluble in more alkaline pH

              Protect from light

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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.