trimethoprim; TMP (Proloprim, Trimpex)
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Introduction
Tradenames: Prolorpin, Trimpex.
Indications
- bacterial infections due to susceptible organisms[5]
- urinary tract infections
- acute otitis media in children
- acute exacerbations of chronic bronchitis in adults
- Pneumocystis carinii pneumonia (PCP)
Dosage
- 100 mg PO BID or 200 mg PO QD
- PCP: 15 mg/kg/day in divided doses given with sulfamethoxazole or dapsone
Tabs: 100 & 200 mg.
Dosage adjustment in renal failure
Table
| creatinine clearance | dosage |
|---|---|
| > 50-90 mL/min | 12 hour dosing |
| 10-50 mL/min* | 18 hour dosing |
| < 10 mL/min# | 24 hour dosing, not recommended[4] |
* same dose for continuous arteriovenous hemofiltration
# dose after hemodialysis Moderately dialyzable: 20-50%
Pharmacokinetics
- rapidly & extensively absorbed
- time to peake serum concentration 1-4 hours
- partially metabolized in liver
- 60-80% excreted unchanged in the urine
- 1/2life 11 hours (20-49 hours ESRD)
elimination via kidney
protein binding = 42-60 %
elimination by hemodialysis = -
Monitor
Therapeutic range:
Antimicrobial activity
- Enterobacter[5]
- Escherichia coli
- Klebsiella
- Proteus
- Staphylococcus aureus
- Haemophilus influenzae
- Streptococcus[5]
Adverse effects
- common (> 10%)
- rash
- pruritus
- less common (1-10%)
- uncommon (< 1%)
- fever, exfoliative dermatitis, nausea/vomiting, epigastric distress, cholestatic jaundice, thrombocytopenia, neutropenia, leukopenia, increased LFTs, increased serum creatinine* & BUN
- hyperkalemia & acute kidney injury[7]
* trimethoprim can increase serum creatinine up to 0.5 mg/dL
- this increase is not associated with loss of renal function[6] (see test interaction)
Drug interactions
- renin-angiotensin-aldosterone system inhibitor in combination further increases risk of hyperkalemia & acute kidney injury[7]
- drug interaction(s) of antibiotics with warfarin
- drug interaction(s) of ARB with trimethoprim
- drug interaction(s) of ACE inhibitor with trimethoprim
- drug interaction(s) of spironolactone with trimethoprim
Test interactions
- serum creatinine:
- trimethoprim inhibits tubular secretion of creatinine
- trimethoprim can increase serum creatinine up to 0.5 mg/dL*
* this increase is not associated with loss of renal function[6]
Mechanism of action
- inhibits synthesis of tetrahydrofolate by inhibiting dihydrofolate reductase, thus inhibiting microbial growth
More general terms
Component of
- sulfamethazine/trimethoprim
- sulfadiazine/trimethoprim
- phenazopyridine/sulfamethoxazole/trimethoprim
- polymixin-B/trimethoprim (Polytrim)
- trimethoprim/sulfamethoxazole; cotrimoxazole (Bactrim, Septra, Cotrim, Sulfatrim, Sulfoxatrim, Trisulfam, Uroplus)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Department of Veterans Affairs, VA National Formulary
- ↑ Jump up to: 4.0 4.1 Geriatric Dosage Handbook, 6th edition, Selma et al eds, Lexi-Comp, Cleveland, 2001
- ↑ Jump up to: 5.0 5.1 5.2 5.3 Deprecated Reference
- ↑ Jump up to: 6.0 6.1 6.2 Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015
- ↑ Jump up to: 7.0 7.1 7.2 Crellin E, Mansfield KE, Leyrat C et al. Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: Cohort study. BMJ 2018 Feb 9; 360:k341 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29438980 Free PMC Article <Internet> http://www.bmj.com/content/360/bmj.k341