Trimethoprim

Brand names: Primsol®Proloprim®

Chemical formula:

Drug Forms:
• Trimethoprim Oral tablet (below)
• Trimethoprim Oral solution

Español:
• Trimetoprima, Tableta oral
• Trimetoprima, Solución oral

Trimethoprim Oral tablet

What is this medicine?

TRIMETHOPRIM is an antibiotic. It is used to treat certain kinds of bacterial infections. It will not work for colds, flu, or other viral infections.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•anemia
•kidney disease
•liver disease
•poor nutrition
•an unusual or allergic reaction to trimethoprim, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I use this medicine?

Take this medicine by mouth with a full glass of water. Follow the directions on the prescription label. Take your medicine at regular intervals. Do not take your medicine more often than directed. Do not skip doses or stop your medicine early even if you feel better. Do not stop taking except on your doctor's advice.

Talk to your pediatrician regarding the use of this medicine in children. While this drug may be prescribed for selected conditions, precautions do apply.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

Do not take this medicine with any of the following medications:
•dofetilide

This medicine may also interact with the following medications:
•ACE inhibitors like benazepril, enalapril, lisinopril, moexipril, quinapril, ramipril, and others
•dapsone
•digoxin
•fluorouracil
•MAOIs like Carbex, Eldepryl, Marplan, Nardil, and Parnate
•phenytoin
•procainamide
•pyrimethamine
•some diuretics
•trimetrexate
•warfarin

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor or health care professional as directed. Tell your doctor if your symptoms do not improve.

This medicine can make you more sensitive to the sun. Keep out of the sun. If you cannot avoid being in the sun, wear protective clothing and use a sunscreen. Do not use sun lamps or tanning beds/booths.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•fast or irregular heartbeat, chest pain
•fever or chills, sore throat
•bluish fingernails or lips
•difficulty breathing
•redness, blistering, peeling or loosening of the skin, including inside the mouth
•unusual bleeding or bruising
•unusually weak or tired

Side effects that usually do not require medical attention (report to your doctor if they continue or are bothersome):
•aches or pains
•changes in taste
•diarrhea
•headache
•nausea, vomiting
•stomach pain

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store at room temperature between 15 and 25 degrees C (59 and 77 degrees F). Protect from light and moisture. Keep container tightly closed. Throw away any unused medicine after the expiration date.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

An antibacterial closely related to pyrimethamine; administered in combination with a sulfonamide because these drugs blockade two consecutive steps in the synthesis of tetrahydrofolate by microorganisms. See also sulfadiazine–trimethoprim.

Trimethoprim
Systematic (IUPAC) name
5-(3,4,5- trimethoxybenzyl) pyrimidine- 2,4- diamine
Identifiers
CAS number	738-70-5
ATC code	J01EA01 QJ51EA01
PubChem	5578
DrugBank	APRD00103
ChemSpider	5376
Chemical data
Formula	C14H18N4O3
Mol. mass	290.32 g/mol
Pharmacokinetic data
Bioavailability	90–100%
Metabolism	hepatic
Half life	8–10 hours
Excretion	renal 50–60%
Therapeutic considerations
Pregnancy cat.	B3(AU) C(US)
Legal status	Prescription Only (S4)(AU) POM(UK)
Routes	Oral

Trimethoprim (INN) (pronounced /traɪˈmɛθəprɪm/) is a bacteriostatic antibiotic mainly used in the prophylaxis and treatment of urinary tract infections. It belongs to the class of chemotherapeutic agents known as dihydrofolate reductase inhibitors. Trimethoprim was formerly marketed by GlaxoSmithKline under trade names including Proloprim, Monotrim and Triprim; but these trade names have been licensed to various generic pharmaceutical manufacturers. In clinical use it is often abbreviated TRI or TMP; its common laboratory abbreviation is W.

Contents 1 Mechanism of action 2 Co-trimoxazole 3 Clinical indications 4 Contraindications and reactions 5 References 6 External links

Mechanism of action

Tetrahydrofolate synthesis pathway

Trimethoprim acts by interfering with the action of bacterial dihydrofolate reductase, inhibiting synthesis of tetrahydrofolic acid. Tetrahydrofolic acid is an essential precursor in the de novo synthesis of the intermediate Thymidine monophosphate (dTMP), precursor of DNA metabolite Thymidine triphosphate^[1]. Bacteria are unable to take up folic acid from the environment (i.e. the infection host) and are thus dependent on their own de novo synthesis. Inhibition of the enzyme starves the bacteria of nucleotides necessary for DNA replication.

Co-trimoxazole

Trimethoprim was commonly (since 1969 in the UK) used in a 1:5 combination with sulfamethoxazole, a sulfonamide antibiotic, which inhibits an earlier step in the folate synthesis pathway (see diagram above). This combination, also known as co-trimoxazole, TMP-sulfa, or TMP-SMX, results in an in vitro synergistic antibacterial effect by inhibiting successive steps in folate synthesis. This claimed benefit was not seen in general clinical use.^{[2] [3]} The combinations use has been declining due to reports of sulfamethoxazole bone marrow toxicity, resistance and lack of greater efficacy in treating common urine and chest infections,^[4][5][6][7] and side effects of antibacterial sulfonamides. As a consequence, the use of co-trimoxazole was restricted in 1995 ^[8] following the availability of trimethoprim (not in combination) in 1980. With its greater efficacy against a limited number of bacteria, Co-trimoxazole remains indicated for some infections; for example, it is used as prophylaxis in patients at risk for Pneumocystis jirovecii pneumonia (e.g. AIDS patients and those with some hematological malignancies) and as therapy in Whipple's disease.

Clinical indications

Trimethoprim, used as monotherapy (since 1980 in the UK), is indicated for the prophylaxis and treatment of urinary tract infections. (Co-trimoxazole, with its greater efficacy against a limited number of bacteria, remains indicated for some infections; (see above))

Contraindications and reactions

Use of trimethoprim is contraindicated during pregnancy, especially the first trimester, and for sufferers of certain blood disorders.^[9] It may be involved in a reaction similar to disulfiram when alcohol is consumed after it is used, particularly when used in combination with sulfamethoxazole.^[10][11] Trimethoprim can also reduce clearance of creatinine at renal tubules.

References

1. ^ de novo synthesis pathway for dTTP[[1]]
2. ^ Brumfitt W, Hamilton-Miller JM (December 1993). "Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines". J Chemother 5 (6): 465–9. PMID 8195839. 
3. ^ Brumfitt W, Hamilton-Miller JM (February 1994). "Limitations of and indications for the use of co-trimoxazole". J Chemother 6 (1): 3–11. PMID 8071675. 
4. ^ Bean DC, Livermore DM, Papa I, Hall LM (November 2005). "Resistance among Escherichia coli to sulphonamides and other antimicrobials now little used in man". J Antimicrob Chemother 56 (5): 962–4. doi:10.1093/jac/dki332. PMID 16150859. http://jac.oxfordjournals.org/cgi/content/full/56/5/962. 
5. ^ Felmingham D, Reinert RR, Hirakata Y, Rodloff A (September 2002). "Increasing prevalence of antimicrobial resistance among isolates of Streptococcus pneumoniae from the PROTEKT surveillance study, and compatative in vitro activity of the ketolide, telithromycin". J Antimicrob Chemother 50 (Suppl S1): 25–37. doi:10.1093/jac/dkf808 (inactive 2008-06-26). PMID 12239226. http://jac.oxfordjournals.org/cgi/reprint/50/suppl_2/25. 
6. ^ Johnson JR, Manges AR, O'Bryan TT, Riley LW (Jun 29 2002). "A disseminated multidrug-resistant clonal group of uropathogenic Escherichia coli in pyelonephritis". Lancet 359 (9325): 2249–51. doi:10.1016/S0140-6736(02)09264-4. PMID 12103291. 
7. ^ Lawrenson RA, Logie JW (December 2001). "Antibiotic failure in the treatment of urinary tract infections in young women". J Antimicrob Chemother 48 (6): 895–901. doi:10.1093/jac/48.6.895. PMID 11733475.  - suggest some small advantage in UTIs
8. ^ "Co-trimoxazole use restricted". Drug Ther Bull 33 (12): 92–3. December 1995. doi:10.1136/dtb.1995.331292. PMID 8777892. 
9. ^ "Trimethoprim". netdoctor.co.uk. http://www.netdoctor.co.uk/medicines/100002648.html. 
10. ^ Edwards DL, Fink PC, Van Dyke PO (17 Feb 1986). "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole". J Clinical pharmacy 5 (12): 999. http://cat.inist.fr/?aModele=afficheN&cpsidt=8287529. 
11. ^ Heelon MW, White M (17 Feb 1998). "Disulfiram-cotrimoxazole reaction". J Pharmacotherapy 18 (4): 869. http://cat.inist.fr/?aModele=afficheN&cpsidt=2340043. 

External links

• Nucleic acid inhibitors (PDF file).

v • d • e Antibacterials: nucleic acid inhibitors (J01E, J01M) Antifolates (inhibits purine metabolism, thereby inhibiting DNA and RNA synthesis) DR inhibitor 2,4-Diaminopyrimidine (Trimethoprim#, Brodimoprim, Tetroxoprim, Iclaprim†) Sulfonamides (DS inhibitor) Short- acting Sulfaisodimidine · Sulfamethizole · Sulfadimidine · Sulfapyridine · Sulfafurazole · Sulfanilamide (Prontosil) · Sulfathiazole · Sulfathiourea Intermediate- acting Sulfamethoxazole · Sulfadiazine# · Sulfamoxole Long- acting Sulfadimethoxine · Sulfalene · Sulfametomidine · Sulfametoxydiazine · Sulfamethoxypyridazine · Sulfaperin · Sulfamerazine · Sulfaphenazole · Sulfamazone Other/ungrouped sulfanilamide (Sulfacetamide, Sulfametrole) Combinations Sulfamethoxazole and trimethoprim# Topoisomerase inhibitors/ quinolones/ (inhibits DNA replication) 1st generation Cinoxacin‡ · Flumequine · Nalidixic acid · Oxolinic acid · Pipemidic acid · Piromidic acid · Rosoxacin Fluoroquinolones 2nd generation Ciprofloxacin#  · Enoxacin‡ · Fleroxacin‡ · Lomefloxacin · Nadifloxacin · Ofloxacin · Norfloxacin · Pefloxacin · Rufloxacin 3rd generation Balofloxacin · Grepafloxacin‡ · Levofloxacin · Pazufloxacin · Sparfloxacin‡ · Temafloxacin‡ · Tosufloxacin 4th generation Besifloxacin · Clinafloxacin† · Garenoxacin · Gemifloxacin · Moxifloxacin · Gatifloxacin‡ · Sitafloxacin · Trovafloxacin‡/Alatrofloxacin‡ · Prulifloxacin Veterinary Danofloxacin · Difloxacin · Enrofloxacin · Ibafloxacin · Marbofloxacin · Orbifloxacin · Pradofloxacin · Sarafloxacin Related agents (DG) Aminocoumarins: Novobiocin Anaerobic DNA inhibitors Nitro- imidazole derivatives Metronidazole#  · Tinidazole · Ornidazole Nitrofuran derivatives Nitrofurantoin#  · Nifurtoinol RNA synthesis Rifamycins/ RNA polymerase Rifampicin · Rifabutin · Rifapentine · Rifaximin #WHO-EM. ‡Withdrawn from market. CLINICAL TRIALS: †Phase III. §Never to phase III

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