Trimethoprim-sulfamethoxazole

Background

• Sulfonamide antibiotic
• Brand names: Septra, Bactrim (US), Sulfatrim, TMP-SMX

Dosing

• Traditionally based on the trimethroprim component

Form	TMP	SMX	Conversion
Intravenous	16 mg/ml	80 mg/ml	10 mL
Oral suspension	8 mg/ml	40 mg/ml	20 mL
Oral SS tab	80 mg	400 mg	2 tabs
Oral DS tab	160 mg	800 mg	1 tab

• Resistant Gram-negative infections
  • Cystitis or pyelonephritis: 160 mg/800 mg (1 DS tab) IV/PO q12h
  • Other infections: 8 to 12 mg/kg/day IV/PO divided q8-12h (max 960 mg total daily dose)
• Nocardia: 10 mg/kg TDD
• Pneumocystis jirovecii
  • Treatment: 15-20 mg/kg TDD
  • Prophylaxis: DS tab once daily; or SS tab once daily; or DS tab three times weekly
• CNS infections: 15-20 mg/kg TDD

Oral Dosing

• Ranges from 1 SS tab BID (160 mg TMP TDD) to 3 DS tabs TID (1440 mg TMP TDD)

Intravenous Dosing

• 10 to 20 mg/kg TMP total daily dose, split TID to QID

Dosing Tables

By Weight

Dose (TMP)	Weight (kg)	Total dose TMP (mg/day)	Dose (IV)	Dose (PO)
10 mg/kg	40-49	480	10 mL q8h	1 DS tab q8h
	50-64	640	10 mL q6h	1 DS tab q6h, or 2 DS tabs q12h
	65-74	720	15 mL q8h	3 SS tabs q8h
	75-99	960	15 mL q6h	2 DS tabs q8h, or 3 SS tabs q6h
	100-129	1280	20 mL q6h	2 DS tabs q6h
15 mg/kg	40-44	640	10 mL q6h	1 DS tab q6h, or 2 DS tabs q12h
	45-49	720	15 mL q8h	3 SS tabs q8h
	50-69	960	15 mL q6h	2 DS tabs q8h, or 3 SS tabs q6h
	70-79	1200	25 mL q8h	5 SS tabs q8h
	80-89	1280	20 mL q6h	2 DS tabs q6h
	90-99	1440	30 mL q8h	3 DS tabs q8h
	100-109	1600	25 mL q6h	2/2/3/3 DS tabs q6h, or 5 SS tabs q6h
	110-119	1680	35 mL q8h	7 SS tabs q8h
	120-129	1920	30 mL q6h	3 DS tabs q6h
20 mg/kg	40-54	960	15 mL q6h	2 DS tabs q8h, or 3 SS tabs q6h
	55-69	1280	20 mL q6h	2 DS tabs q6h
	70-79	1440	30 mL q8h	3 DS tabs q8h
	80-89	1600	25 mL q6h	2/2/3/3 DS tabs q6h, or 5 SS tabs q6h
	90-104	1920	30 mL q6h	3 DS tabs q6h
	105-119	2240	35 mL q6h	3/3/4/4 DS tabs q6h, or 7 SS tabs q6h
	120-134	2560	40 mL q6h	4 DS tabs q6h

By Regimen

Regimen	Total dose TMP (mg/day)
1 SS q12h	160 mg
1 SS q8h	240 mg
1 DS q12h	320 mg
1 DS q8h	480 mg
1 DS q6h	640 mg
2 DS q12h
3 SS q8h	720 mg
2 DS q8h	960 mg
5 SS q8h	1200 mg
2 DS q6h	1280 mg
3 DS q8h	1440 mg
5 SS q6h	1600 mg
7 SS q8h	1680 mg
7 SS q6h	2240 mg
4 DS q6h	2560 mg

Renal Dosing

CrCl (mL/min)	Bacterial infection (TMP)	PJP (TMP)
> 30	8-12 mg/kg/day in 2-4 divided doses	15-20 mg/kg/day in 2-4 divided doses
10 to 29	75% of usual dose	12-15 mg/kg/day in 2-4 divided doses
< 10, including PD	Generally not recommended; use 50% of usual dose	Generally not recommended; use 7.5-10 mg/kg/day in 2-4 divided doses
Hemodialysis	50% of usual dose, scheduled post-dialysis	50% of usual dose, scheduled post-dialysis
CRRT	7.5 mg/kg/day in 2-4 divided doses	15 mg/kg/day in 2-4 divided doses

Safety

Adverse Drug Reactions

• Systemic allergic reactions
  • Anaphylaxis
  • Serum sickness
• Cutaneous reactions
  • High rate of SJS/TEN
  • Other non-specific rash
  • Erythema multiforme
  • Urticaria
  • Photodermatitis
• GI upset, including nausea at higher doses
• Drug-drug interactions
  • Increases warfarin levels
• Anemia, neutropenia and thrombocytopenia
  • It is a mild folate antagonist
• Hepatotoxicity
• Hyperkalemia
• Hyponatremia
• Hypoglycemia
• Acute kidney injury, though it also increases tubular creatinine reabsorption
• Renal tubular acidosis

Pregnancy

• Relatively contraindicated, should only be used when no alternative exists
• When used in first trimester:
  • Suspected increase in risk of spontaneous abortion[1]
  • Possible increase in neural tube defects and other congenital malformations when used in first trimester[2]
• Mostly theoretical increase in kernicterus when used in third trimester, close to delivery[3]

Further Reading

• Considerations when prescribing trimethoprim-sulfamethoxazole. CMAJ. 2011;183(16):1851-1858. doi: 10.1503/cmaj.111152
  • Review of adverse events