Drug reference

Cotrimoxazole

Sulfonamide · Antibiotic

Also known as Trimethoprim/Sulfamethoxazole, SMX/TMP, Co-trimoxazole, Bactrim, Septra

SulfonamideAntibioticATC J01EE01

CDSCO approvedSchedule HJan AushadhiNPPA price-controlledATC J01EE01

Pharmacokineticsplasma · t hours

ONSET: 1.5h · Oral: 1-2 hours
PEAK: 2.5h · Oral: 1-4 hours
t½: 9h · Trimethoprim: 8-10 hours; Sulfamethoxazole: 9-11 hours
DURATION: 12h · Approximately 12 hours

EXCRETION

—

not curated

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

Generally avoided, especially in the first trimester due to potential folate antagonism (Trimethoprim) and in the third trimester due to kernicterus risk in neonates (Sulfamethoxazole). Use only if potential benefit outweighs risk.

FDA category + note

Top interactionssee all 12 →

ChlorthalidoneSevereTextbook-citedKDT 7e · p948
DesogestrelSevereTextbook-citedKDT 7e · p948
EthinylestradiolSevereTextbook-citedKDT 7e · p948
GlibenclamideSevereTextbook-citedKDT 7e · p948

Mechanism

Cotrimoxazole works by sequentially blocking two steps in bacterial folic acid synthesis. Sulfamethoxazole inhibits bacterial dihydropteroate synthase, preventing para-aminobenzoic acid (PABA) incorporation into dihydrofolic acid. Trimethoprim inhibits bacterial dihydrofolate reductase, preventing the reduction of dihydrofolic acid to tetrahydrofolic acid, a crucial cofactor for DNA and protein synthesis. This synergistic blockade leads to bactericidal activity.

Indications

Urinary Tract Infections (UTIs)Acute Otitis MediaAcute Exacerbations of Chronic BronchitisTraveler's DiarrheaPneumocystis Jirovecii Pneumonia (PJP/PCP) prophylaxis and treatmentNocardiosisStenotrophomonas Maltophilia infectionsToxoplasmosis (off-label)Some community-acquired MRSA skin and soft tissue infections (off-label)Prophylaxis for catheterization or instrumentation of urinary tractProphylaxis for recurrences of UTIProphylaxis for Pneumocystis jiroveci pneumoniaurinary tract infections (acute, uncomplicated, chronic, recurrent, prostatitis)respiratory tract infections (upper, lower, chronic bronchitis, facio-maxillary infections, otitis media by gram-positive cocci and H. influenzae)bacterial diarrhoeas and dysentery (severe and invasive infections by E. coli, Shigella, nontyphoid Salmonella, and Y. enterocolitica)pneumocystis jiroveci pneumonia (in neutropenic and AIDS patients, both prophylactic and therapeutic)chancroid (third choice alternative)typhoid (historically, but now unreliable)protecting agranulocytosis patientstreating respiratory or other infections in agranulocytosis patientssepticaemias (intensive parenteral therapy)uncomplicated acute UTI (empirically)prophylaxis of recurrent cystitis in womenprophylaxis in catheterized patientschancroid (alternative)

Dosing

Adult: Standard dose (e.g., for UTIs): 160 mg Trimethoprim/800 mg Sulfamethoxazole orally every 12 hours. PCP treatment: 15-20 mg/kg/day Trimethoprim component (and 75-100 mg/kg/day Sulfamethoxazole) orally or IV divided into 3-4 doses. PCP prophylaxis: 160 mg Trimethoprim/800 mg Sulfamethoxazole orally once daily or three times weekly.
Pediatric: Dosing is based on the Trimethoprim component, generally 8-12 mg/kg/day (TMP) divided every 12 hours for infections; 15-20 mg/kg/day (TMP) for PCP treatment. Not recommended for infants less than 2 months of age.
Renal adjustment: CrCl 15-30 mL/min: Reduce dose by 50% or extend dosing interval to every 24 hours. CrCl <15 mL/min: Not recommended unless plasma concentrations can be monitored; if used, reduce dose by 75% or give 50% of dose every 24 hours.
Hepatic adjustment: Use with caution. Generally not recommended in severe hepatic impairment due to increased risk of cholestasis and hepatotoxicity. Dose reduction may be necessary in moderate impairment.
Geriatric: Increased risk of severe adverse reactions including bone marrow suppression, hypersensitivity, and hyperkalemia. Use with caution, monitor renal function closely, and consider lower initial doses.
Max dose: Max Trimethoprim 320 mg/day for standard infections; up to 20 mg/kg/day (TMP) for PCP treatment.

Pharmacokinetics

Onset

Oral: 1-2 hours

Peak effect

Oral: 1-4 hours

Duration

Approximately 12 hours

Half-life

Trimethoprim: 8-10 hours; Sulfamethoxazole: 9-11 hours

Bioavailability

Oral: 85-100%

Protein binding

Trimethoprim: 40-50%; Sulfamethoxazole: 60-70%

Metabolism

Hepatic. Sulfamethoxazole undergoes N4-acetylation. Trimethoprim undergoes hydroxylation and oxidation.

Excretion

Primarily renal (glomerular filtration and tubular secretion) as unchanged drug and metabolites.

Contraindications

Hypersensitivity to sulfamethoxazole or trimethoprim or any component
Megaloblastic anemia due to folate deficiency
Severe hepatic parenchymal disease
Severe renal impairment (CrCl <15 mL/min) if unmonitored
Infants younger than 2 months of age (risk of kernicterus)
Porphyria
Concurrent use with dofetilide
Pregnancy (increased risk to foetus)
pregnancy (theoretical teratogenic risk, neonatal haemolysis and methaemoglobinaemia near term)
newborns (risk of kernicterus)
pregnancy (for UTI treatment)

Side effects

Common

NauseaVomitingDiarrheaAnorexiaSkin rash (including photosensitivity)HyperkalemiaElevated transaminasesstomatitisheadacherashesfever (up to 50% in AIDS patients on high dose)skin rash (up to 50% in AIDS patients on high dose)

Serious

Stevens-Johnson syndrome
Toxic Epidermal Necrolysis (TEN)
Agranulocytosis
Aplastic anemia
Thrombocytopenia
Hemolytic anemia (especially in G6PD deficiency)
Pseudomembranous colitis
Drug-induced liver injury
Acute kidney injury
Severe hypersensitivity reactions
Aseptic meningitis
Crystalluria
haemolysis (in G-6PD deficient individuals)
higher incidence of adverse reactions in AIDS patients
folate deficiency (megaloblastic anaemia, infrequent, in patients with marginal folate levels)
blood dyscrasias (rare)
uremia (in patients with renal disease)
bone marrow hypoplasia (up to 50% in AIDS patients on high dose)
bone marrow toxicity (greater risk in the elderly)
thrombocytopenia (higher incidence with diuretics)

Pregnancy & lactation

Pregnancy

Lactation

Both components are excreted into breast milk. Contraindicated in infants with G6PD deficiency, hyperbilirubinemia, or those under 2 months of age due to risk of kernicterus. Use with caution for other infants.