SULMEPRIM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SULMEPRIM (SULMEPRIM).

How it works

Sulmeprim is a combination of sulfamethoxazole, a sulfonamide, and trimethoprim, a dihydrofolate reductase inhibitor. It inhibits sequential steps in bacterial folate synthesis, leading to bactericidal activity.

What the body does with it

Metabolism	Sulfamethoxazole is metabolized primarily via N-acetylation and glucuronidation; trimethoprim is metabolized via oxidative pathways and conjugation. Both are substrates of CYP2C9 and CYP3A4.
Excretion	Renal excretion of unchanged drug accounts for 70% of elimination; 20% is metabolized in the liver to inactive metabolites (glucuronide conjugates) and excreted in urine; 10% is eliminated in feces via biliary excretion.
Half-life	Terminal elimination half-life is 10-12 hours in patients with normal renal function, allowing twice-daily dosing. In severe renal impairment (CrCl <30 mL/min), half-life extends to >20 hours, requiring dose adjustment.
Protein binding	Approximately 40-50% bound to plasma proteins, primarily albumin.
Volume of Distribution	0.3-0.5 L/kg, indicating distribution primarily into extracellular fluid and well-perfused tissues. Achieves therapeutic concentrations in lung, kidney, and prostate tissue.
Bioavailability	Oral: 90-100% (well absorbed). Intravenous: 100%.
Onset of Action	Oral: 1-2 hours; Intravenous: 15-30 minutes.
Duration of Action	12 hours (consistent with half-life). Dosing interval is typically 12 hours; for more severe infections, 8-hourly intervals may be used.

Classification & Brands

Dosing & administration

Adults: 800 mg sulfamethoxazole/160 mg trimethoprim (one double-strength tablet) orally every 12 hours for 10-14 days. For severe infections or pneumonia, intravenous dose: 15-20 mg/kg/day (based on trimethoprim component) divided every 6-8 hours.

Dosage form	SUSPENSION
Renal impairment	CrCl >30 mL/min: no adjustment. CrCl 15-30 mL/min: reduce dose by 50% (e.g., single-strength tablet every 12 hours). CrCl <15 mL/min: contraindicated except for prophylaxis of Pneumocystis jirovecii pneumonia? If necessary, use 50% dose and monitor levels; generally avoid.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: use with caution, monitor liver function; dose reduction not specified. Child-Pugh C: contraindicated due to risk of hepatotoxicity and altered metabolism.
Pediatric use	Children >2 months: 6-12 mg/kg/day trimethoprim and 30-60 mg/kg/day sulfamethoxazole divided every 12 hours. For Pneumocystis jirovecii pneumonia treatment: 15-20 mg/kg/day trimethoprim divided every 6-8 hours.
Geriatric use	Elderly patients: start at lower end of dosing range due to age-related renal impairment; monitor renal function and adjust based on CrCl. Avoid use with ACE inhibitors or potassium-sparing diuretics due to hyperkalemia risk. Use with caution if concurrent medications that increase K+.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for SULMEPRIM (SULMEPRIM).

Breastfeeding	Sulfadiazine excreted in breast milk; M/P ratio approximately 0.5. Avoid in infants with G6PD deficiency or jaundice due to risk of hemolysis and kernicterus. Use with caution; alternative preferred.
Teratogenic Risk	First trimester: Sulfadiazine crosses placenta; potential for neural tube defects due to folate antagonism. Second/third trimester: Risk of kernicterus in neonates due to bilirubin displacement from albumin. Avoid near term.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Sulfonamides, including sulfamethoxazole, have been associated with severe adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Use with caution in patients with hepatic or renal impairment, folate deficiency, or hypersensitivity to sulfonamides.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Hypersensitivity to sulfonamides or trimethoprim","Megaloblastic anemia due to folate deficiency","Severe hepatic or renal impairment (CrCl <15 mL/min)","Pregnancy (especially first trimester) and lactation","Infants less than 2 months of age","Concurrent use with dofetilide"]

Clinical Precautions

Precautions

["Risk of severe hypersensitivity reactions including SJS/TEN","Hematological toxicity (thrombocytopenia, agranulocytosis, aplastic anemia)","Hepatic necrosis","Renal toxicity and crystalluria","Hyperkalemia in patients with renal impairment or on potassium-sparing diuretics","Folate deficiency and megaloblastic anemia with prolonged use","Photosensitivity","Disulfiram-like reaction with alcohol"]

Clinical Tips & Counseling

Drug interactions

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SULMEPRIM

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SULMEPRIM (SULMEPRIM).

How it works

What the body does with it

Metabolism	Sulfamethoxazole is metabolized primarily via N-acetylation and glucuronidation; trimethoprim is metabolized via oxidative pathways and conjugation. Both are substrates of CYP2C9 and CYP3A4.
Excretion	Renal excretion of unchanged drug accounts for 70% of elimination; 20% is metabolized in the liver to inactive metabolites (glucuronide conjugates) and excreted in urine; 10% is eliminated in feces via biliary excretion.
Half-life	Terminal elimination half-life is 10-12 hours in patients with normal renal function, allowing twice-daily dosing. In severe renal impairment (CrCl <30 mL/min), half-life extends to >20 hours, requiring dose adjustment.
Protein binding	Approximately 40-50% bound to plasma proteins, primarily albumin.
Volume of Distribution	0.3-0.5 L/kg, indicating distribution primarily into extracellular fluid and well-perfused tissues. Achieves therapeutic concentrations in lung, kidney, and prostate tissue.
Bioavailability	Oral: 90-100% (well absorbed). Intravenous: 100%.
Onset of Action	Oral: 1-2 hours; Intravenous: 15-30 minutes.
Duration of Action	12 hours (consistent with half-life). Dosing interval is typically 12 hours; for more severe infections, 8-hourly intervals may be used.

Classification & Brands

Dosing & administration

Dosage form	SUSPENSION
Renal impairment	CrCl >30 mL/min: no adjustment. CrCl 15-30 mL/min: reduce dose by 50% (e.g., single-strength tablet every 12 hours). CrCl <15 mL/min: contraindicated except for prophylaxis of Pneumocystis jirovecii pneumonia? If necessary, use 50% dose and monitor levels; generally avoid.
Liver impairment	Child-Pugh A: no adjustment. Child-Pugh B: use with caution, monitor liver function; dose reduction not specified. Child-Pugh C: contraindicated due to risk of hepatotoxicity and altered metabolism.
Pediatric use	Children >2 months: 6-12 mg/kg/day trimethoprim and 30-60 mg/kg/day sulfamethoxazole divided every 12 hours. For Pneumocystis jirovecii pneumonia treatment: 15-20 mg/kg/day trimethoprim divided every 6-8 hours.
Geriatric use	Elderly patients: start at lower end of dosing range due to age-related renal impairment; monitor renal function and adjust based on CrCl. Avoid use with ACE inhibitors or potassium-sparing diuretics due to hyperkalemia risk. Use with caution if concurrent medications that increase K+.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for SULMEPRIM (SULMEPRIM).

Breastfeeding	Sulfadiazine excreted in breast milk; M/P ratio approximately 0.5. Avoid in infants with G6PD deficiency or jaundice due to risk of hemolysis and kernicterus. Use with caution; alternative preferred.
Teratogenic Risk	First trimester: Sulfadiazine crosses placenta; potential for neural tube defects due to folate antagonism. Second/third trimester: Risk of kernicterus in neonates due to bilirubin displacement from albumin. Avoid near term.
Fetal Monitoring