Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ACEPHEN vs BACTRIM
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
ACEPHEN (acetaminophen) is a para-aminophenol derivative with analgesic and antipyretic activity. Its mechanism involves inhibition of cyclooxygenase (COX) enzymes in the central nervous system, particularly COX-2, reducing prostaglandin synthesis. It has weak peripheral COX inhibition and minimal anti-inflammatory effect.
BACTRIM (sulfamethoxazole/trimethoprim) inhibits bacterial folate synthesis. Sulfamethoxazole, a sulfonamide, inhibits dihydropteroate synthase, blocking PABA incorporation into dihydrofolic acid. Trimethoprim inhibits dihydrofolate reductase, blocking conversion of dihydrofolic acid to tetrahydrofolic acid. Sequential blockade leads to bactericidal effect.
Mild to moderate pain,Fever
Urinary tract infections,Acute otitis media,Acute exacerbations of chronic bronchitis,Traveler's diarrhea,Shigellosis,Pneumocystis jirovecii pneumonia (treatment and prophylaxis),Toxoplasmosis (prophylaxis in immunocompromised),Nocardia infections,Methicillin-resistant Staphylococcus aureus (MRSA) infections (off-label)
325-650 mg orally every 4-6 hours as needed; maximum 4 g/day.
1 DS tablet (160 mg TMP/800 mg SMX) orally every 12 hours for 10-14 days.
Terminal elimination half-life: 1.0-1.5 hours in adults with normal renal function. Prolonged to 2-5 hours in hepatic impairment or elderly; requires dose adjustment in severe hepatic disease.
Sulfamethoxazole: 9-12 hours (prolonged in renal impairment); Trimethoprim: 8-10 hours (prolonged in renal impairment).
Acetaminophen is primarily metabolized in the liver via glucuronidation (UGT1A1, UGT1A6, UGT1A9) and sulfation (SULT1A1, SULT1A3). A minor fraction is oxidized by cytochrome P450 enzymes (CYP2E1, CYP1A2, CYP3A4) to a reactive toxic metabolite (NAPQI), which is normally detoxified by conjugation with glutathione.
Sulfamethoxazole is metabolized primarily via N-acetylation in the liver (N-acetyltransferase-2, NAT2). Trimethoprim is metabolized via O-demethylation and alpha-hydroxylation by cytochrome P450 (CYP) enzymes, mainly CYP3A4, with minor contribution from CYP1A2 and CYP2C9.
Renal: 90-95% as unchanged drug; tubular secretion and glomerular filtration. Biliary/fecal: <5%.
Renal: sulfamethoxazole 20-30% unchanged, trimethoprim 40-70% unchanged; biliary/fecal: minimal (<10%) for both components.
Approximately 10-20% bound to serum albumin; extensive tissue binding.
Sulfamethoxazole: 70% bound to albumin; Trimethoprim: 30-40% bound to albumin.
Apparent Vd: 0.5-0.7 L/kg (30-40 L in a 70 kg adult). Distributions into CSF and breast milk.
Sulfamethoxazole: 0.21 L/kg; Trimethoprim: 1.8 L/kg (high tissue penetration including lung, kidney, and CSF).
Oral: 85-90% (first-pass metabolism minimal). Rectal: approximately 70-80% of oral bioavailability.
Oral: 100% for both components (well absorbed).
GFR 10-50 m L/min: 650 mg every 6 hours; GFR <10 m L/min: 650 mg every 8 hours.
Cr Cl >30 m L/min: No adjustment. Cr Cl 15-30 m L/min: 50% of standard dose. Cr Cl <15 m L/min: Contraindicated.
Child-Pugh Class A: no adjustment; Child-Pugh Class B: maximum 2 g/day; Child-Pugh Class C: maximum 1 g/day.
Child-Pugh Class A: No adjustment. Child-Pugh Class B: Use with caution, monitor for toxicity; consider dose reduction. Child-Pugh Class C: Avoid use.
10-15 mg/kg/dose orally every 4-6 hours; maximum 75 mg/kg/day or 4 g/day, whichever is less.
8 mg/kg/day TMP / 40 mg/kg/day SMX in two divided doses every 12 hours (max 320 mg TMP/1600 mg SMX per day). For PCP treatment: 15-20 mg/kg/day TMP / 75-100 mg/kg/day SMX in 3-4 divided doses.
Start at lowest effective dose (325 mg every 6 hours); avoid exceeding 3 g/day unless closely monitored.
Initiate at lower doses; monitor renal function closely; contraindicated if Cr Cl <15 m L/min; adjust based on Cr Cl (see renal adjustment).
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product.
BACTRIM may cause life-threatening severe adverse reactions including: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Discontinue at first sign of skin rash or any sign of adverse reaction. Hypersensitivity reactions can occur even with re-challenge of the same or other sulfonamides.
Risk of severe liver injury with doses >4000 mg/day; use caution with hepatic impairment, chronic alcoholism, malnutrition, or concomitant hepatotoxic drugs; avoid exceeding recommended dose; limit use to 10 days for pain or 3 days for fever unless directed by physician; serious skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) have occurred.
Fatal hypersensitivity reactions including SJS/TEN,Hepatotoxicity and hepatic failure,Blood dyscrasias (leukopenia, thrombocytopenia, agranulocytosis),Clostridioides difficile-associated diarrhea,Renal impairment: risk of crystalluria; maintain adequate fluid intake,Hyperkalemia in patients with renal disease or on potassium-sparing drugs,Megaloblastic anemia in folate-deficient patients,Elderly patients at increased risk of severe adverse reactions,Pregnancy: avoid near term due to risk of kernicterus (sulfonamide displaces bilirubin),Lactation: caution; sulfonamides excreted in breast milk,Photosensitivity
Hypersensitivity to acetaminophen or any component of the formulation; severe hepatic impairment or active liver disease.
Hypersensitivity to sulfonamides, trimethoprim, or any component,History of drug-induced immune thrombocytopenia with sulfonamides or trimethoprim,Megaloblastic anemia due to folate deficiency,Severe hepatic or renal impairment (Cr Cl <15 m L/min),Pregnancy at term and during breastfeeding,Infants less than 2 months of age,Combination with dofetilide (increased risk of torsades de pointes)
Alcohol: increased risk of hepatotoxicity. Avoid concurrent use. Food: no significant interaction, but taking with food may reduce minor gastrointestinal irritation.
Avoid high-potassium foods (bananas, oranges, potatoes) if hyperkalemia is a concern. No specific food interactions; however, maintain adequate fluid intake to prevent crystalluria.
Pregnancy Category C. First trimester: potential risk of neural tube defects and orofacial clefts (limited human data, animal studies show embryotoxicity). Second and third trimesters: NSAID exposure associated with oligohydramnios, premature ductus arteriosus constriction, and fetal renal impairment. Avoid in third trimester.
Pregnancy Category D. First trimester: Folate antagonist; associated with neural tube defects, cardiovascular malformations, and cleft palate. Second and third trimesters: Risk of kernicterus in neonates due to displacement of bilirubin from albumin; may cause hemolytic anemia in G6PD-deficient fetuses. Avoid use, especially near term.
Excreted into breast milk in low concentrations (M/P ratio approximately 0.10). Considered compatible with breastfeeding; however, use lowest effective dose for shortest duration given potential for neonatal adverse effects (e.g., thrombocytopenia, renal dysfunction).
Both trimethoprim and sulfamethoxazole are excreted into breast milk. M/P ratio not well defined. Potential for kernicterus in jaundiced or G6PD-deficient infants; may interfere with folate metabolism. Caution advised; consider alternative therapy.
No standard dose adjustments recommended; however, due to increased plasma volume and metabolism in pregnancy, higher doses may be required to achieve therapeutic effect. Avoid near term.
Trimethoprim-sulfamethoxazole dose generally unchanged but avoid in first trimester and near term. If unavoidable, consider increased folate supplementation. No specific pharmacokinetic-driven dose adjustment established; monitor clinical response and adjust based on renal function.
ACEPHEN (acetaminophen) is commonly used for mild to moderate pain and fever. Avoid exceeding 4 g/day in adults to prevent hepatotoxicity. In patients with hepatic impairment, reduce maximum daily dose to 2 g. Consider acetylcysteine for overdose. Onset of action is 15-30 minutes orally.
Bactrim is contraindicated in G6PD deficiency due to risk of hemolytic anemia. Monitor renal function and potassium levels, especially in elderly patients, as sulfamethoxazole can cause hyperkalemia. Use with caution in patients with folic acid deficiency or megaloblastic anemia. Avoid in pregnancy at term and in lactating women due to risk of kernicterus. For PCP treatment, high doses may require leucovorin rescue to prevent bone marrow suppression.
Do not exceed 4000 mg (4 grams) in 24 hours.,Avoid drinking alcohol while taking this medication.,Do not combine with other products containing acetaminophen.,Take with food if stomach upset occurs.,Seek immediate medical help if you experience symptoms of liver damage: yellowing of skin/eyes, dark urine, severe abdominal pain.
Take with a full glass of water and stay well-hydrated to prevent crystalluria.,Complete the full course even if symptoms improve.,Report any signs of allergic reaction (rash, fever, sore throat) or severe skin reactions (blistering, peeling).,Avoid prolonged sun exposure; use sunscreen as photosensitivity may occur.,Do not take if you have a history of sulfa allergy or are pregnant/nursing without consulting doctor.
No interactions on record
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about ACEPHEN vs BACTRIM, answered by our medical review team.
ACEPHEN is a Non-Opioid Analgesic that works by ACEPHEN (acetaminophen) is a para-aminophenol derivative with analgesic and antipyretic activity. Its mechanism involves inhibition of cyclooxygenase (COX) enzymes in the central nervous system, particularly COX-2, reducing prostaglandin synthesis. It has weak peripheral COX inhibition and minimal anti-inflammatory effect.. BACTRIM is a Sulfonamide Antibiotic Combination that works by BACTRIM (sulfamethoxazole/trimethoprim) inhibits bacterial folate synthesis. Sulfamethoxazole, a sulfonamide, inhibits dihydropteroate synthase, blocking PABA incorporation into dihydrofolic acid. Trimethoprim inhibits dihydrofolate reductase, blocking conversion of dihydrofolic acid to tetrahydrofolic acid. Sequential blockade leads to bactericidal effect.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ACEPHEN and BACTRIM depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of ACEPHEN is: 325-650 mg orally every 4-6 hours as needed; maximum 4 g/day.. The standard adult dose of BACTRIM is: 1 DS tablet (160 mg TMP/800 mg SMX) orally every 12 hours for 10-14 days.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between ACEPHEN and BACTRIM in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. ACEPHEN is classified as Category C. Pregnancy Category C. First trimester: potential risk of neural tube defects and orofacial clefts (limited human data, animal studies show embryotoxicity). Second and third trimest. BACTRIM is classified as Category C. Pregnancy Category D. First trimester: Folate antagonist; associated with neural tube defects, cardiovascular malformations, and cleft palate. Second and third trimesters: Risk of . Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.