Methenamine

This article is about methenamine as a medication. For methenamine as a chemical in general, see Hexamethylenetetramine.
Methenamine
Clinical data
Pronunciationmeh-THEH-na-meen[1]
Trade namesHiprex, Urex, Urotropin, others
Other namesHexamethylenetetramine; HMTA; Hexamine; Hexamethylenamine; Hexamethyleneamine; Metenamine; Urometine; Hippramine; E-239; R-657; 1,3,5,7-Tetraazaadamantane
Routes of
administration		Oral[2][3][4]
Drug classAntiseptic; Antibacterial
ATC code
Pharmacokinetic data
BioavailabilityHigh (≥70%)[5][6][2]
Protein bindingUnknown[3]
MetabolismHydrolysis in acidic urine[3]
Metabolites• Formaldehyde[3][7]
• Ammonia[3][7]
• Formic acid[8][9]
Onset of action≤30 minutes[3][4]
Elimination half-life2–6 hours[2][5][3]
ExcretionUrine: 70–90% unchanged within 24 hours[3]
Identifiers
  • 1,3,5,7-tetrazatricyclo[3.3.1.13,7]decane
CAS Number
PubChem CID
PubChem SID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC6H12N4
Molar mass140.190 g·mol−1
3D model (JSmol)
  • C1N2CN3CN1CN(C2)C3
  • InChI=1S/C6H12N4/c1-7-2-9-4-8(1)5-10(3-7)6-9/h1-6H2 checkY
  • Key:VKYKSIONXSXAKP-UHFFFAOYSA-N checkY

Methenamine, also known as hexamine or hexamethylenetetramine and sold under the brand names Hiprex, Urex, and Urotropin among others, is a urinary tract antiseptic and antibacterial medication which is used in the prevention of recurrent urinary tract infections (UTIs).[4][3][1][6][10] It is not an antibiotic, and unlike antibiotics, has no risk of bacterial resistance.[7][11][6] Methenamine can reduce the risk of UTIs by 44 to 86% and has been found to be non-inferior to low-dose prophylactic antibiotics.[10][12][13] It is taken by mouth.[3][6] The drug is available both by prescription and at lower doses over the counter.[2][14][4][15]

Side effects of methenamine are minor and infrequent and include upset stomach, nausea, and headache.[3][16][5] Methenamine is a prodrug of formaldehyde in acidic urine.[3][6][7] Formaldehyde is a non-specific antiseptic and bactericide which works via denaturation of bacterial proteins and nucleic acids.[2][3][6][7] Conversion of methenamine into formaldehyde only occurs in acidic environments and hence its actions show selectivity for tissues like the bladder and stomach.[6][17] Chemically, methenamine is a simple cyclized hydrocarbon and is similar in structure to adamantane.[11][5][6]

Methenamine was discovered in 1859[5] and was first introduced for medical use as a urinary antiseptic in 1895.[18][19] It was formally approved for medical use in the United States in 1967.[20] Though it became a "forgotten drug" following the discovery of antibiotics in 1928, there has been a resurgence in interest in methenamine since 2010 owing to increasing rates of bacterial resistance with antibiotics.[2][6][5][12][21] Larger and higher-quality clinical trials of methenamine for UTI prevention have started to be published in the 2020s and it may soon be recommended by more medical guidelines.[2][12][16][22][13] Methenamine has been found to be more cost-effective than low-dose prophylactic antibiotics for preventing UTIs.[23]

  1. ^ a b "Methenamine Uses, Side Effects & Warnings". Drugs.com. 20 May 2024. Retrieved 11 October 2024.
  2. ^ a b c d e f g Cite error: The named reference LiCoslerHarausz2024 was invoked but never defined (see the help page).
  3. ^ a b c d e f g h i j k l m "Methenamine: Uses, Interactions, Mechanism of Action". DrugBank Online. 31 December 1993. Retrieved 11 October 2024.
  4. ^ a b c d https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/017681Orig1s019lbl.pdf
  5. ^ a b c d e f Cite error: The named reference AltinozOzpinarOzpinar2019 was invoked but never defined (see the help page).
  6. ^ a b c d e f g h i Cite error: The named reference LoHammerZegarra2014 was invoked but never defined (see the help page).
  7. ^ a b c d e Cite error: The named reference ChwaKavanaghLinnebur2019 was invoked but never defined (see the help page).
  8. ^ Cite error: The named reference RestaniRestelliGalli1992 was invoked but never defined (see the help page).
  9. ^ Cite error: The named reference DreyforsJonesSayed1989 was invoked but never defined (see the help page).
  10. ^ a b Cite error: The named reference LeeBhutaSimpson2012 was invoked but never defined (see the help page).
  11. ^ a b Sihra N, Goodman A, Zakri R, Sahai A, Malde S (December 2018). "Nonantibiotic prevention and management of recurrent urinary tract infection". Nat Rev Urol. 15 (12): 750–776. doi:10.1038/s41585-018-0106-x. PMID 30361493.
  12. ^ a b c Gu C, Ackerman AL (June 2023). "An oldie but a goodie: Methenamine as a nonantibiotic solution to the prevention of recurrent urinary tract infections". PLOS Pathog. 19 (6): e1011405. doi:10.1371/journal.ppat.1011405. PMC 10270343. PMID 37319137.
  13. ^ a b Cite error: The named reference HardingMossopHomer2022 was invoked but never defined (see the help page).
  14. ^ Brodin, M. (1998). The Over-The-Counter Drug Book. Pocket Books. p. 182. ISBN 978-0-671-01380-6. Retrieved 11 October 2024.
  15. ^ "Search Results for methenamine". DailyMed. 2 February 2016. Retrieved 11 October 2024.
  16. ^ a b Cite error: The named reference DavidsonBrownNance2024 was invoked but never defined (see the help page).
  17. ^ Cite error: The named reference AriënsHanselaarHenderson1982 was invoked but never defined (see the help page).
  18. ^ Cite error: The named reference Hinman1913 was invoked but never defined (see the help page).
  19. ^ Cite error: The named reference MedReview1896 was invoked but never defined (see the help page).
  20. ^ Cite error: The named reference Sauberan2018 was invoked but never defined (see the help page).
  21. ^ Kale S, Somani BK (November 2023). "The resurgence of methenamine hippurate in the prevention of recurrent UTIs in women- a systematic review". Curr Opin Urol. 33 (6): 488–496. doi:10.1097/MOU.0000000000001108. PMID 37337660.
  22. ^ Cite error: The named reference KwokMcGoergeMayer-Coverdale2022 was invoked but never defined (see the help page).
  23. ^ King W, Homer T, Harding C, Mossop H, Chadwick T, Abouhajar A, Vale L (April 2024). "Cost-effectiveness of methenamine hippurate compared with antibiotic prophylaxis for the management of recurrent urinary tract infections in secondary care: a multicentre, open-label, randomised, non-inferiority trial". BMJ Open. 14 (4): e074445. doi:10.1136/bmjopen-2023-074445. PMC 11086477. PMID 38684270.