Reviewed on 6/20/2022

What Is Trimethoprim/Sulfamethoxazole and How Does It Work?

Trimethoprim/Sulfamethoxazole is a prescription medication used to treat the symptoms of infections such as Chronic Bronchitis, Bacterial Meningitis, Pneumocystis jiroveci pneumonia (PCP), Sepsis, Shigellosis, Traveler’s Diarrhea and Urinary Tract Infections.

Trimethoprim/Sulfamethoxazole is available under the following different brand names: Bactrim, Bactrim DS, Septra, Septra DS, Cotrim, Cotrimoxazole, Sulfatrim

What Are Side Effects Associated with Using Trimethoprim/Sulfamethoxazole?

  • Common side effects of Trimethoprim/Sulfamethoxazole include:
    • nausea, 
    • vomiting, 
    • loss of appetite, and
    • skin rash
  • Serious side effects of Trimethoprim/Sulfamethoxazole include:
    • hives, 
    • cough, 
    • chest pain, 
    • shortness of breath, 
    • swelling in your face or throat, 
    • fever, 
    • sore throat
    • burning eyes, 
    • skin pain, 
    • red or purple skin rash with blistering and peeling, 
    • swollen glands, 
    • muscle aches, 
    • severe weakness, 
    • pale skin, 
    • unusual bruising, 
    • yellowing of your skin or eyes, 
    • severe stomach pain, 
    • diarrhea that is watery or bloody (even if it occurs months after your last dose), 
    • skin rash (no matter how mild), 
    • seizure
    • new or unusual joint pain, 
    • increased or decreased urination, 
    • swelling, bruising, or irritation around the IV needle, 
    • increased thirst, 
    • dry mouth
    • fruity breath odor, 
    • new or worsening cough, 
    • trouble breathing, 
    • nausea, 
    • weakness, 
    • tingly feeling, 
    • chest pain, 
    • irregular heartbeats, 
    • loss of movement, 
    • headache, 
    • confusion, 
    • slurred speech, 
    • vomiting, 
    • loss of coordination, 
    • feeling unsteady, 
    • chills, 
    • mouth sores, 
    • skin sores, 
    • easy bruising, 
    • unusual bleeding, 
    • pale skin, 
    • cold hands and feet, and
    • lightheadedness
  • Rare side effects of Trimethoprim/Sulfamethoxazole include:
    • none 

This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088

Dosages of Trimethoprim/Sulfamethoxazole

Adult Dosages

Injected Solution

  • (16 mg/80 mg)/mL 

Oral Suspension

  • (40 mg/200 mg)/5 mL


  • 80 mg/400 mg
  • 160 mg/800 mg

Pediatric Dosages

Mild to Moderate Infections

  • Not indicated for children younger than 2 months of age
  • 8 mg orally twice daily

Serious Infections

  • Not indicated for children younger than 2 months of age
  • 15-20 mg orally four times daily
  • 8-12 mg divided every two to four times daily via IV 

Acute Ear Infection (Otitis Media)

  • Not indicated for children younger than 2 months of age
  • 6-10 mg orally divided twice daily for 10 days

Pneumocystis (Carinii) Jiroveci Pneumonia

  • Not indicated for children younger than 2 months of age
  • Treatment: 15-20 mg orally or via IV every 6-8 hours for 21 days
  • Prophylaxis: 150 mg orally divided every 12 hours for 3 days per week into consecutive or alternative days


  • Not indicated for children younger than 2 months of age
  • 8 mg orally divided every 12 hours for 5 days
  • 8-10 mg via IV divided every 6-12 hours for 5 days

Urinary Tract Infection

  • Not indicated for children younger than 2 months of age
  • 8 mg orally divided every 12 hours for 7-14 days for serious infection
  • 8-10 mg via IV divided every 6-12 hours for 14 days for serious infection
  • Prophylaxis: 2 mg orally daily or 5 mg twice weekly 

Dosage Considerations – Should be Given as Follows: 

  • See “Dosages”.

What Other Drugs Interact with Trimethoprim/Sulfamethoxazole?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them.  Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first

  • Trimethoprim/Sulfamethoxazole has no known severe interactions with other drugs
  • Trimethoprim/Sulfamethoxazole has serious interactions with at least 56 other drugs
  • Trimethoprim/Sulfamethoxazole has moderate interactions with at least 191 other drugs  
  • Trimethoprim/Sulfamethoxazole has mild interactions with at least 131 other drugs

This information does not contain all possible interactions or adverse effects.  Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use.  Keep a list of all your medications with you, and share this information with your doctor and pharmacist.  Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

What Are Warnings and Precautions for Trimethoprim/Sulfamethoxazole?

Keep out of reach of children.  In case of overdose, get medical help or contact a Poison Control Center immediately


  • Known hypersensitivity
  • Not for use in children younger than 2 months of age
  • Creatinine clearance below 15 ml/min when renal function status cannot be monitored
  • Documented megaloblastic or folate deficiency anemia
  • Significant liver impairment
  • Pregnant patients at term and nursing mothers, 
  • History of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides
  • Concomitant administration with dofetilide

Effects of drug abuse

  • None

Short-Term Effects

  • See “What Are Side Effects Associated with Using Trimethoprim/Sulfamethoxazole?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Trimethoprim/Sulfamethoxazole?”


  • Not for use in areas with resistance rates >10%
  • Severe and symptomatic hyponatremia can occur in patients receiving sulfamethoxazole/ trimethoprim, particularly for the treatment of pneumocystis jirovecii pneumonia; evaluation for hyponatremia and appropriate correction is necessary for symptomatic patients to prevent life-threatening complications
  • If a patient treated for Pneumocystis jirovecii develops a skin rash, fever, leukopenia, or any other sign of an 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 a 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), 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 the first appearance of skin rash or any sign of serious adverse reaction
  • Acute and delayed lung injury; anaphylaxis and circulatory shock have occurred with the administration of sulfamethoxazole and trimethoprim products
  • Cough, shortness of breath, and pulmonary infiltrates potentially represent hypersensitivity reactions of the respiratory tract reported in association with sulfamethoxazole and trimethoprim treatment
  • Severe pulmonary adverse reactions occurring within days to a week of initiation of treatment and resulting in prolonged respiratory failure requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO), lung transplantation, or death are 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 were 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 the absence of strongly suspected bacterial infection or a 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 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) is 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 the 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 for the treatment of Pneumocystis jirovecii pneumonia, monitor for total daily intake of propylene glycol from all sources and 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 the 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
    • A high dosage of trimethoprim, as used in patients with P Pneumocystis 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 jirovecii pneumonia
  • AIDS patients may not tolerate or respond to sulfamethoxazole/trimethoprim in the 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 Pneumocystis jirovecii pneumonia, was reported to be increased compared with incidence normally associated with the use of the drug in non-AIDS patients
  • If a patient develops a skin rash, fever, leukopenia, or any sign of an adverse reaction, reevaluate the benefit-risk of continuing therapy or re-challenge with a drug

Pregnancy and Lactation

  • Therapy may cause fetal harm if administered to pregnant women; some epidemiologic studies suggest that exposure to drugs during pregnancy may be associated with an 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, pre-eclampsia, and increased mortality in a pregnant woman
  • Pneumocystis jirovecii pneumonia in pregnancy is associated with preterm birth and increased morbidity and mortality for the pregnant woman
  • Use during pregnancy only if the potential benefit justifies the potential risk to the fetus
  • Levels of drugs 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 the effect of therapy on breastfed infants or the effect on milk production; because of the potential risk of bilirubin displacement and kernicterus on the breastfed child, advise women to avoid breastfeeding during therapy
Medscape. Trimethoprim/Sulfamethoxazole.

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