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Bactrim

GENERAL
Take with food/liquids, stay well hydrated
1/2-life: 10h (SMX), 11h (TMP)
Peak Effect: 2-3h (SMX); 4h (TMP)
Excretion: 25% urinary unchanged (SMX); 40% to 75% urinary unchanged (TMP)
SUSCEPTIBILITIES
Proteus, E. coli, Klebsiella, Enterobacter, Morganella
MONITORING
Renal function tests if renal impairment. Renal function tests and CBC monitoring if on long term therapy.
MECHANISM
​Inhibit formation of folate (tetrahydrofolic acid). SMX is similar to para-aminobenzoic acid (PABA) and competes to bind dihydropteroate synthetase which form dihydrofolic acid, an intermediate in folate synthesis.TMP inhibits bacterial dihydrofolate reeducates to inhibit late synthesis.
MEDICATION INTERACTIONS
coNTRAINDICATIONS
Sulfa allergy
Severe hepatic insufficiency or parenchymal damage 
Severe renal insufficiency (CrCl less than 15 mL/min) when renal function status cannot be monitored
Drug-induced immune thrombocytopenia 
Megaloblastic anemia secondary to folate deficiency and other blood dyscrasias or severe hematological disorders
Premature infants
Pregnancy or breastfeeding
In combination with dofetilide 
Treatment of streptococcal pharyngitis 
Infants less than 4 months of age (kernicterus)
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency of glucose-galactose malabsorption
Acute porphyria
WARNINGS/PRECAUTIONS
May induce photosensitivity
Steven's Johnson
Teratogenic
Use with caution if thyroid dysfunction
Reported association w/ C. diff 
Long term use may cause bone marrow depression
Hemolysis possible in dose related manner in glucose-6-phosphate dehydrogenase deficient patients
Trimethoprim induced reported hyperkalmeia
Hyponatremia can occur w/ TMP-SMX
Folate deficiency
Hypoglycemia
SIDE EFFECTS
VERY COMMON >10% : Hyperkalemia, headache
COMMON 1-10%: Rash, urticarial, diarrhea, nausea, vomiting, anorexia, thrush, acute kidney injury
RARE <0.1%: Thrombophlebitis, jaundice, rhabdomyolysis (mainly in AIDS patients)
VERY RARE <.01%: Polyarteritis nodosa, syncope, photosensitivity, Steven's Johnson Syndrome, constipation, glossitis, stomatitis, pseudomembranous colitis, pancreatitis, abdominal pain, bone marrow suppression, hepatitis, elevated LFT's, anaphylaxis, hypoglycemia, hyponatremia, metabolic acidosis, sseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, dizziness, tremor, lethargy, paresthesia, convulsions, peripheral neuritis, tinnitus, uveitis, depression, hallucination, confusional state, agitation, anxiety, abnormal behavior, insomnia, nightmares, renal tubular acidosis, hematuria, renal failure, cough, dyspnea, lung infiltration, shortness of breath, wheezing, epistaxis
DOSAGE
ADULT: Double Strength (DS) is 800mg/160mg SMX-TMP
UTI -PO SMX-TMP DS q12h x10-14d
PYELONEPHRITIS: SMX-TMP DS po q12h x10-14d

UTI PROPHYLAXIS: SMX-TMP DS po q24h or 3x weekly at bedtime or postcoitally
PROSTATITIS: SMX-TMP DS po q12h x10-14d (acute) or x1-3mo (chronic)
PEDIATRIC:
UTI: 2 months or older:4 mg/kg po q12h x10-14d 
RENAL DOSING: 
CrCl < 15 mL/min - Contraindicated
CrCl 15 to 30 mL/min - 50% dose reduction
CrCl > 30 mL/min - No dose reduction
HEPATIC DOSING
Severe hepatic impairment - Contraindication
Mild to moderate hepatic impairment - Caution
DIALYSIS
Peritoneal dialysis not effective and HD somewhat effective in eliminating trimethoprim (TMP) and sulfamethoxazole (SMX). Give after HD because of this.
INTERESTING STUDIES
AKI from Bactrim - A retrospective study of 178,238 patients 65 yrs and over with a cumulative 422,514 UTI episodes treated with antibiotics showed trimethoprim has odds ratio of 1.72 for association with AKI in the 14 days after therapy compared w/ amoxicillin and OR of 2.27 for hyperkalemia. This suggests for 1000 UTI's treated with trimethoprim would result in 1-2 additional cases of hyperkalemia and 2 admissions with AKI, compared to amoxicillin.  If patients were taking ARB/ACE and spironolactone, there were 18 additional cases of hyperkalemia and 11 admissions w/ AKI. There was no association with increase risk of death. ​(1)
  1. Crellin, Elizabeth, et al. "Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study." bmj 360 (2018): k341.
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