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Sulfamethoxazole and Trimethoprim to Antibiotics

Sulfamethoxazole/Trimethoprim (Co-trimoxazole)

Mechanism: Sulfamethoxazole/trimethoprim (SMX/TMP, co-trimoxazole; brand names Bactrim, Septra) is a fixed 5:1 combination of a sulfonamide (sulfamethoxazole) and a dihydrofolate reductase inhibitor (trimethoprim). Together they block two sequential steps in bacterial folate synthesis: SMX (a PABA analogue) inhibits dihydropteroate synthase, and TMP inhibits dihydrofolate reductase. This synergistic blockade is often bactericidal rather than merely bacteriostatic.. Both components are well absorbed orally, achieve good tissue and cerebrospinal fluid levels, and are eliminated by the kidneys. The TMP/SMX ratio is usually 1:5 by weight (e.g. 80 mg TMP + 400 mg SMX, or double-strength tablets 160/800 mg).

Uses

SMX/TMP has very broad antibacterial coverage (many Gram-positive and Gram-negative pathogens) and multiple clinical uses. It is a first-line or alternative therapy for:

  • Urinary tract infections (UTIs): e.g. cystitis, pyelonephritis, and chronic bacterial prostatitis. It is also used for suppression of recurrent UTIs.
  • Respiratory infections: such as acute otitis media and bacterial bronchitis. (It is not effective for viral infections like colds or flu.)
  • Gastrointestinal infections: including traveler’s diarrhea, shigellosis (bacillary dysentery), Vibrio cholerae, Campylobacter, etc.
  • Pneumocystis jirovecii pneumonia (PCP): SMX/TMP is the drug of choice for treatment and prophylaxis of PCP in immunocompromised patients (HIV/AIDS, cancer, transplant).
  • Skin/soft tissue infections: It covers community-associated MRSA and other skin infections caused by susceptible strains.

Other important uses include therapy or prophylaxis of certain opportunistic/parasitic infections: e.g. Cyclospora, Cystoisospora and Toxoplasma gondii enteritis, and mild nocardiosis. It also has activity against Nocardia and Listeria (used when these organisms are identified).

SMX/TMP effectively treats many infections, especially UTIs, PCP prophylaxis, and resistant skin or GI pathogens.

Forms and Dosing

SMX/TMP is available orally (tablets and suspension) and intravenously (IV) for severe infections.. Common oral strengths are single-strength (SMX 400 mg/ TMP 80 mg) and double-strength (SMX 800 mg/ TMP 160 mg) tablets. A typical adult dose for uncomplicated UTI is one double-strength tablet twice daily (5–14 days). For PCP treatment, much higher doses are used (e.g. TMP 15–20 mg/kg/day, often given as multiple DS tablets every 6–8 hours, or IV equivalent). Chronic suppressive doses (e.g. one tablet daily or a few times per week) may be used for prophylaxis of recurrent UTIs or PCP. Dosage must be adjusted in renal impairment (TMP/SMX is renally cleared) and in infants/small children by weight.

Adults swallow tablets with plenty of water (to reduce crystalluria risk). Adequate hydration is advised during therapy. (The suspension form allows pediatric dosing.) The 1:5 dosing ratio (TMP:SMX) should always be maintained; do not alter the tablet ratio. IV SMX/TMP is used when patients cannot take oral drugs or in life-threatening infections.

Side Effects and Adverse Reactions

As with other sulfa drugs, adverse effects of SMX/TMP can affect multiple organ systems:

  • Gastrointestinal: Nausea, vomiting, anorexia, diarrhea and abdominal pain are common. Take with food if intolerable.
  • Skin reactions: Rash, itching and photosensitivity are frequent. Sulfa hypersensitivity can rarely cause severe reactions like Stevens–Johnson syndrome/toxic epidermal necrolysis (blistering, peeling skin). Patients with HIV/AIDS have especially high rates of dermatologic and other reactions..
  • Hematologic: Bone marrow suppression may occur. SMX/TMP can cause pancytopenia (anemia, leukopenia, thrombocytopenia) and notably macrocytic anemia due to folate antagonism. Folate or folinic acid supplementation may be needed for prolonged therapy.
  • Electrolyte: Trimethoprim acts like a potassium‐sparing diuretic; it can raise serum potassium, sometimes to dangerous levels. Monitor electrolytes during high-dose or long-term use.
  • Renal: Interstitial nephritis is a potential effect of sulfonamides. Trimethoprim also yields a reversible rise in serum creatinine (by inhibiting its tubular secretion) even without true GFR decline. Kidney function should be monitored, especially in elderly or dehydrated patients. Crystalluria and obstruction can occur if dehydrated (drink fluids).
  • Other: Headache, dizziness, and fatigue are reported. Rarely, hepatic necrosis and drug-induced aseptic meningitis have been described. Transient hyperbilirubinemia and elevated LFTs can occur.

Most side effects are related to sulfonamide toxicity. Nausea and rash are the most common. Patients on high-dose therapy (especially HIV patients) should be monitored closely.

Precautions and Contraindications

  • Sulfa allergy: Contraindicated in patients with a known allergy to sulfonamides. A history of severe sulfa reaction (e.g. SJS) is an absolute contraindication.
  • Age: Avoid in infants <2 months old (risk of kernicterus). (SMX displaces bilirubin.) Pediatric use is acceptable for ≥2 months with appropriate dosing.
  • Pregnancy/Breastfeeding: Avoid during first trimester (neural tube defect risk) and near term (kernicterus risk). Sulfonamides cross the placenta and may cause fetal harm; if used in pregnancy, folate supplementation is recommended. Breastfeeding is usually discouraged (sulfamethoxazole is excreted in milk).
  • Renal/Hepatic impairment: Use with caution in renal or liver dysfunction. Dose reduction is required for renal insufficiency. Avoid in severe renal failure unless necessary (risk of accumulation/toxicity).
  • Blood disorders: Use cautiously in patients with folate deficiency or blood dyscrasias (anemia, neutropenia). Baseline CBC and periodic monitoring are prudent for long courses.
  • Drug interactions: SMX/TMP inhibits CYP2C9 and other pathways. It potentiates warfarin (increased INR/bleeding risk) and phenytoin/methotrexate levels. It enhances the hypoglycemic effect of sulfonylureas. Check drug levels/INR when coadministered.
  • Hydration: Ensure adequate fluids to prevent crystalluria. Clamp IV lines if needed.
  • Other caution: Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may risk hemolysis with sulfonamides (exercise caution).

Summary

Sulfamethoxazole/trimethoprim (co-trimoxazole) is a broad-spectrum antibiotic combination that blocks bacterial folate synthesis in two steps. Its spectrum covers many Gram-positive and Gram-negative bacteria (including some MRSA) and certain protozoa/fungi. Clinically, it is widely used for UTIs, PCP pneumonia (prophylaxis and treatment), respiratory and GI infections, and resistant organisms. Therapy is usually oral (DS tablets or suspension) but IV formulations exist for severe cases. Patients must be monitored for classic sulfonamide toxicities: GI upset, rash, hematologic suppression, renal effects, and hyperkalemia. Use is contraindicated in sulfa-allergic individuals and should be avoided in neonates and pregnancy due to fetal risks. All prescribing should follow physician guidance and official guidelines for dosing and monitoring.

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Sulfamethoxazole/Trimethoprim (Co-trimoxazole)

Mechanism: Sulfamethoxazole/trimethoprim (SMX/TMP, co-trimoxazole; brand names Bactrim, Septra) is a fixed 5:1 combination of a sulfonamide (sulfamethoxazole) and a dihydrofolate reductase inhibitor (trimethoprim). Together they block two sequential steps in bacterial folate synthesis: SMX (a PABA analogue) inhibits dihydropteroate synthase, and TMP inhibits dihydrofolate reductase. This synergistic blockade is often bactericidal rather than merely bacteriostatic.. Both components are well absorbed orally, achieve good tissue and cerebrospinal fluid levels, and are eliminated by the kidneys. The TMP/SMX ratio is usually 1:5 by weight (e.g. 80 mg TMP + 400 mg SMX, or double-strength tablets 160/800 mg).

Uses

SMX/TMP has very broad antibacterial coverage (many Gram-positive and Gram-negative pathogens) and multiple clinical uses. It is a first-line or alternative therapy for:

  • Urinary tract infections (UTIs): e.g. cystitis, pyelonephritis, and chronic bacterial prostatitis. It is also used for suppression of recurrent UTIs.
  • Respiratory infections: such as acute otitis media and bacterial bronchitis. (It is not effective for viral infections like colds or flu.)
  • Gastrointestinal infections: including traveler’s diarrhea, shigellosis (bacillary dysentery), Vibrio cholerae, Campylobacter, etc.
  • Pneumocystis jirovecii pneumonia (PCP): SMX/TMP is the drug of choice for treatment and prophylaxis of PCP in immunocompromised patients (HIV/AIDS, cancer, transplant).
  • Skin/soft tissue infections: It covers community-associated MRSA and other skin infections caused by susceptible strains.

Other important uses include therapy or prophylaxis of certain opportunistic/parasitic infections: e.g. Cyclospora, Cystoisospora and Toxoplasma gondii enteritis, and mild nocardiosis. It also has activity against Nocardia and Listeria (used when these organisms are identified).

SMX/TMP effectively treats many infections, especially UTIs, PCP prophylaxis, and resistant skin or GI pathogens.

Forms and Dosing

SMX/TMP is available orally (tablets and suspension) and intravenously (IV) for severe infections.. Common oral strengths are single-strength (SMX 400 mg/ TMP 80 mg) and double-strength (SMX 800 mg/ TMP 160 mg) tablets. A typical adult dose for uncomplicated UTI is one double-strength tablet twice daily (5–14 days). For PCP treatment, much higher doses are used (e.g. TMP 15–20 mg/kg/day, often given as multiple DS tablets every 6–8 hours, or IV equivalent). Chronic suppressive doses (e.g. one tablet daily or a few times per week) may be used for prophylaxis of recurrent UTIs or PCP. Dosage must be adjusted in renal impairment (TMP/SMX is renally cleared) and in infants/small children by weight.

Adults swallow tablets with plenty of water (to reduce crystalluria risk). Adequate hydration is advised during therapy. (The suspension form allows pediatric dosing.) The 1:5 dosing ratio (TMP:SMX) should always be maintained; do not alter the tablet ratio. IV SMX/TMP is used when patients cannot take oral drugs or in life-threatening infections.

Side Effects and Adverse Reactions

As with other sulfa drugs, adverse effects of SMX/TMP can affect multiple organ systems:

  • Gastrointestinal: Nausea, vomiting, anorexia, diarrhea and abdominal pain are common. Take with food if intolerable.
  • Skin reactions: Rash, itching and photosensitivity are frequent. Sulfa hypersensitivity can rarely cause severe reactions like Stevens–Johnson syndrome/toxic epidermal necrolysis (blistering, peeling skin). Patients with HIV/AIDS have especially high rates of dermatologic and other reactions..
  • Hematologic: Bone marrow suppression may occur. SMX/TMP can cause pancytopenia (anemia, leukopenia, thrombocytopenia) and notably macrocytic anemia due to folate antagonism. Folate or folinic acid supplementation may be needed for prolonged therapy.
  • Electrolyte: Trimethoprim acts like a potassium‐sparing diuretic; it can raise serum potassium, sometimes to dangerous levels. Monitor electrolytes during high-dose or long-term use.
  • Renal: Interstitial nephritis is a potential effect of sulfonamides. Trimethoprim also yields a reversible rise in serum creatinine (by inhibiting its tubular secretion) even without true GFR decline. Kidney function should be monitored, especially in elderly or dehydrated patients. Crystalluria and obstruction can occur if dehydrated (drink fluids).
  • Other: Headache, dizziness, and fatigue are reported. Rarely, hepatic necrosis and drug-induced aseptic meningitis have been described. Transient hyperbilirubinemia and elevated LFTs can occur.

Most side effects are related to sulfonamide toxicity. Nausea and rash are the most common. Patients on high-dose therapy (especially HIV patients) should be monitored closely.

Precautions and Contraindications

  • Sulfa allergy: Contraindicated in patients with a known allergy to sulfonamides. A history of severe sulfa reaction (e.g. SJS) is an absolute contraindication.
  • Age: Avoid in infants <2 months old (risk of kernicterus). (SMX displaces bilirubin.) Pediatric use is acceptable for ≥2 months with appropriate dosing.
  • Pregnancy/Breastfeeding: Avoid during first trimester (neural tube defect risk) and near term (kernicterus risk). Sulfonamides cross the placenta and may cause fetal harm; if used in pregnancy, folate supplementation is recommended. Breastfeeding is usually discouraged (sulfamethoxazole is excreted in milk).
  • Renal/Hepatic impairment: Use with caution in renal or liver dysfunction. Dose reduction is required for renal insufficiency. Avoid in severe renal failure unless necessary (risk of accumulation/toxicity).
  • Blood disorders: Use cautiously in patients with folate deficiency or blood dyscrasias (anemia, neutropenia). Baseline CBC and periodic monitoring are prudent for long courses.
  • Drug interactions: SMX/TMP inhibits CYP2C9 and other pathways. It potentiates warfarin (increased INR/bleeding risk) and phenytoin/methotrexate levels. It enhances the hypoglycemic effect of sulfonylureas. Check drug levels/INR when coadministered.
  • Hydration: Ensure adequate fluids to prevent crystalluria. Clamp IV lines if needed.
  • Other caution: Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may risk hemolysis with sulfonamides (exercise caution).

Summary

Sulfamethoxazole/trimethoprim (co-trimoxazole) is a broad-spectrum antibiotic combination that blocks bacterial folate synthesis in two steps. Its spectrum covers many Gram-positive and Gram-negative bacteria (including some MRSA) and certain protozoa/fungi. Clinically, it is widely used for UTIs, PCP pneumonia (prophylaxis and treatment), respiratory and GI infections, and resistant organisms. Therapy is usually oral (DS tablets or suspension) but IV formulations exist for severe cases. Patients must be monitored for classic sulfonamide toxicities: GI upset, rash, hematologic suppression, renal effects, and hyperkalemia. Use is contraindicated in sulfa-allergic individuals and should be avoided in neonates and pregnancy due to fetal risks. All prescribing should follow physician guidance and official guidelines for dosing and monitoring.

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