Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ACEPHEN vs BACTRIM DS
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 DS is a combination of sulfamethoxazole and trimethoprim. Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA), while trimethoprim inhibits dihydrofolate reductase, blocking reduction of dihydrofolate to tetrahydrofolate. This sequential blockade of folic acid synthesis leads to bactericidal action.
Mild to moderate pain,Fever
FDA-approved: Urinary tract infections, acute otitis media, acute exacerbations of chronic bronchitis, traveler's diarrhea, shigellosis, Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis,Off-label: Methicillin-resistant Staphylococcus aureus (MRSA) infections, Stenotrophomonas maltophilia infections, nocardiosis, Wegener's granulomatosis (as second-line therapy), inflammatory bowel disease
325-650 mg orally every 4-6 hours as needed; maximum 4 g/day.
One double-strength tablet (trimethoprim 160 mg-sulfamethoxazole 800 mg) orally every 12 hours.
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: 8-10 hours; Trimethoprim: 8-12 hours; prolonged in renal impairment (creatinine clearance <30 m L/min: up to 24-48 hours).
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 by N-acetylation and glucuronidation; trimethoprim is metabolized by O-demethylation and N-oxidation. Both are eliminated renally via glomerular filtration and tubular secretion.
Renal: 90-95% as unchanged drug; tubular secretion and glomerular filtration. Biliary/fecal: <5%.
Renal: 50-70% as sulfamethoxazole (unchanged and acetylated metabolite), 40-60% as trimethoprim (unchanged); biliary: <10% for both; fecal: <4%.
Approximately 10-20% bound to serum albumin; extensive tissue binding.
Sulfamethoxazole: 68% bound (albumin); Trimethoprim: 44% bound (albumin, alpha-1-acid glycoprotein).
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: 1.3-1.8 L/kg (wide distribution, higher in tissues than plasma).
Oral: 85-90% (first-pass metabolism minimal). Rectal: approximately 70-80% of oral bioavailability.
Oral: >90% for both components; IV: 100%.
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 usual dose every 12 hours; Cr Cl <15 m L/min: Not recommended.
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, no specific dose recommendation; Child-Pugh Class C: Contraindicated.
10-15 mg/kg/dose orally every 4-6 hours; maximum 75 mg/kg/day or 4 g/day, whichever is less.
Based on trimethoprim component: 8 mg/kg/day of trimethoprim divided every 12 hours. For severe infections, up to 20 mg/kg/day of trimethoprim divided every 6 hours.
Start at lowest effective dose (325 mg every 6 hours); avoid exceeding 3 g/day unless closely monitored.
Monitor renal function; adjust dose based on Cr Cl. Increased risk of hyperkalemia and folate deficiency; consider folate supplementation.
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 DS carries a black box warning for severe hypersensitivity reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and fulminant hepatic necrosis. Also warns about fatal reactions such as agranulocytosis, aplastic anemia, and other blood dyscrasias. Additionally, use in pregnancy at term may cause kernicterus in the newborn.
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.
Hypersensitivity reactions: risk of SJS/TEN, especially in patients with HIV, folate deficiency, or genetic susceptibility (e.g., HLA-B*1502, HLA-A*3101). Discontinue at first sign of rash.,Hematologic toxicity: monitor CBCs; caution in patients with folate deficiency, renal impairment, or prolonged therapy.,Hepatic toxicity: can cause cholestatic jaundice, hepatic necrosis; avoid in hepatic impairment.,Renal toxicity: maintain adequate hydration to prevent crystalluria; adjust dose in renal impairment.,Hyperkalemia: risk with high-dose trimethoprim; monitor potassium, especially in patients with renal dysfunction or on potassium-sparing diuretics.,Hypoglycemia: risk in patients with renal impairment or malnutrition; caution with sulfonylureas.,Photosensitivity: avoid excessive sun exposure.,Pregnancy: avoid at term due to risk of kernicterus; use only if benefit outweighs risk.,Lactation: caution due to potential for kernicterus in infants with G6PD deficiency.
Hypersensitivity to acetaminophen or any component of the formulation; severe hepatic impairment or active liver disease.
Hypersensitivity to sulfamethoxazole, trimethoprim, or any component.,History of drug-induced immune thrombocytopenia with sulfonamides or trimethoprim.,Severe hepatic disease (e.g., acute hepatitis, cirrhosis with jaundice).,Severe renal impairment (Cr Cl <15 m L/min) unless dialysis is available.,Megaloblastic anemia due to folate deficiency.,Pregnancy at term and nursing mothers (due to risk of kernicterus).,Concurrent use with dofetilide (increased risk of arrhythmias).,Infants <2 months of age (sulfonamides can cause kernicterus).
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 (e.g., bananas, oranges, potatoes) as trimethoprim can increase serum potassium. Avoid alcohol, which may cause disulfiram-like reaction (flushing, nausea, tachycardia). No significant food-drug interactions beyond potassium and alcohol.
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.
First trimester: Folate antagonist; associated with neural tube defects, cardiovascular malformations, and cleft palate. Second trimester: Growth restriction, preterm birth. Third trimester: Kernicterus risk due to bilirubin displacement from albumin. Avoid during entire pregnancy.
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).
Breastfeeding safety: Both trimethoprim and sulfamethoxazole are excreted into breast milk; M/P ratio for trimethoprim ~1.25, sulfamethoxazole ~0.15. Caution in infants under 2 months or with G6PD deficiency; theoretical risk of kernicterus.
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.
No standard dose adjustment recommended; avoid use if possible. If necessary, ensure adequate folic acid intake; may need to increase dose due to increased clearance in pregnancy, but specific data lacking.
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 DS (sulfamethoxazole/trimethoprim) is contraindicated in G6PD deficiency due to risk of hemolytic anemia. Monitor for hyperkalemia, especially in elderly or those with renal impairment. Caution with warfarin (potentiates anticoagulation). Avoid in pregnancy (teratogenic) and lactation. Use with caution in folate deficiency; supplement folate if needed.
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.,Avoid prolonged sun exposure; use sunscreen as this drug may cause photosensitivity.,Complete the full course even if you feel better to prevent antibiotic resistance.,Report any skin rash, sore throat, fever, or unusual bleeding immediately.,Do not take if you are pregnant, planning to become pregnant, or breastfeeding.,Inform your doctor if you have kidney disease, G6PD deficiency, or are on blood thinners.
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 DS, 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 DS is a Sulfonamide Antibiotic Combination that works by BACTRIM DS is a combination of sulfamethoxazole and trimethoprim. Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA), while trimethoprim inhibits dihydrofolate reductase, blocking reduction of dihydrofolate to tetrahydrofolate. This sequential blockade of folic acid synthesis leads to bactericidal action.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ACEPHEN and BACTRIM DS 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 DS is: One double-strength tablet (trimethoprim 160 mg-sulfamethoxazole 800 mg) orally every 12 hours.. 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 DS 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 DS is classified as Category C. First trimester: Folate antagonist; associated with neural tube defects, cardiovascular malformations, and cleft palate. Second trimester: Growth restriction, preterm birth. Third . Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.