Methenamine

Identification

Name
Methenamine
Accession Number
DB06799  (DB06146)
Type
Small Molecule
Groups
Approved, Vet approved
Description

Methenamine is a heterocyclic organic compound with a cage-like structure similar to adamantane. In salt form it is used for the treatment of urinary tract infection (Example: methenamine hippurate which is the hippuric acid salt of methenamine).

Structure
Thumb
Synonyms
  • 1,3,5,7-tetraazatricyclo[3.3.1.13,7]decane
  • Hexamethylenamine
  • Hexamethylene tetramine
  • Hexamethylenetetramine
  • Hexamethylentetramin
  • Hexamethylentetraminum
  • Hexamine
  • Hexaminum
  • HMT
  • HMTA
  • metenamina
  • méthénamine
  • methenaminum
External IDs
E-239 / E239 / INS NO.239 / INS-239
Product Ingredients
IngredientUNIICASInChI Key
Methenamine citrateQ4U8R7741634317-08-3UAMIYHCXAONPMG-UHFFFAOYSA-N
Methenamine diphosphateIZP83XSR3072962-49-3BGAZSPYPJDSHIT-UHFFFAOYSA-N
Methenamine hippurateM329791L575714-73-8ROAIXOJGRFKICW-UHFFFAOYSA-N
Methenamine hydrochlorideA3F8KN5WMU24360-05-2NGDSBQHTMKGUQU-UHFFFAOYSA-N
Methenamine mandelate695N30CINR587-23-5UXNFIJPHRQEWRQ-UHFFFAOYSA-N
Methenamine phosphate11G6DJX54Q72962-48-2GJJQWIOYOCDCJA-UHFFFAOYSA-N
Methenamine sulfate0373WW6GZQ19267-18-6CCCDIBJJOMJPQI-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Hip Rex Tab 1gmTablet1 gOralGraceway Pharmaceuticals1993-12-312008-07-16Canada
HiprexTablet1 g/1OralSanofi Aventis1976-09-092018-09-18Us
HiprexTablet1 g/1OralValidus Pharmaceuticals1976-09-09Not applicableUs
MandelamineTablet500 mgOralErfa Canada 2012 Inc1951-12-31Not applicableCanada
Methenamine HippurateTablet1 g/1OralWinthrop U.S.2012-01-232019-05-30Us00955 1037 10 nlmimage10 be44df06
Methenamine HippurateTablet1 g/1OralCounty Line Pharamceuticals2010-05-03Not applicableUs43199 0020 01 nlmimage10 bc3c5e42
Methenamine HippurateTablet1 g/1OralAlvogen, Inc.2010-05-03Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Methenamine HippurateTablet1 g/1OralCarilion Materials Management2003-07-01Not applicableUs68151 098420180907 15195 k7dszx
Methenamine HippurateTablet1 g/1OralAurobindo Pharma Limited2016-07-05Not applicableUs
Methenamine HippurateTablet1 g/1OralLeading Pharma, Llc2016-06-03Not applicableUs
Methenamine HippurateTablet1 g/1OralImpax Generics2003-07-01Not applicableUs
Methenamine HippurateTablet1 g/1OralRising Pharmaceuticals2003-07-012009-09-14Us
Methenamine HippurateTablet1 g/1OralGolden State Medical Supply2003-07-012017-01-02Us64720 0139 10 nlmimage10 473c23c1
Methenamine HippurateTablet1 g/1OralCorePharma, LLC2003-07-012020-02-01Us
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Azo Urinary Tract Defense Antibacterial ProtectionMethenamine (162 mg/1) + Sodium salicylate (162.5 mg/1)TabletOrali-Health, Inc.2015-11-06Not applicableUs
CVS Antibacterial Plus Urinary Pain ReliefMethenamine (162 mg/1) + Sodium salicylate (162.5 mg/1)TabletOralCVS Health2017-02-22Not applicableUs
Cystex PlusMethenamine (162 mg/1) + Sodium salicylate (162.5 mg/1)TabletOralDse Healthcare Solutions, Llc.2012-04-01Not applicableUs
Cystex PlusMethenamine (162 mg/1) + Sodium salicylate (162.5 mg/1)TabletOralClarion Brands, Llc2015-11-01Not applicableUs
Meijer Antibacterial Plus Urinary Pain ReliefMethenamine (162 mg/1) + Sodium salicylate (162.5 mg/1)TabletOralMeijer Distribution2017-02-22Not applicableUs
Methenamine and Sodium SalicylateMethenamine (162 mg/1) + Sodium salicylate (162.5 mg/1)TabletOralAmol Pharmaceuticals Private Limited2015-10-032018-09-06Us
Preferred Antibacterial Plus Urinary Pain ReliefMethenamine (162 mg/1) + Sodium salicylate (162.5 mg/1)TabletOralReese Pharmaceutical Company2017-02-22Not applicableUs
Premier Value Antibacterial Plus Urinary Pain ReliefMethenamine (162 mg/1) + Sodium salicylate (162.5 mg/1)TabletOralChain Drug Consortium2017-02-22Not applicableUs
Quality Choice Antibacterial Plus Urinary Pain ReliefMethenamine (162 mg/1) + Sodium salicylate (162.5 mg/1)TabletOralChain Drug Marketing Association2017-02-22Not applicableUs
Saprolex TabMethenamine mandelate (250 mg) + Methylene blue (10 mg)TabletOralProduits Francais Labs Inc.1982-12-311997-05-30Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Azuphen MbMethenamine (120 mg/1) + Hyoscyamine sulfate dihydrate (0.12 mg/1) + Methylene blue trihydrate (10 mg/1) + Phenyl salicylate (36 mg/1) + Sodium phosphate, monobasic, monohydrate (40.8 mg/1)CapsuleOralBurel Pharmaceuticals, Llc2015-09-282016-11-01Us
DarcalmaMethenamine (81.6 mg/1) + Hyoscyamine sulfate dihydrate (0.12 mg/1) + Methylene blue trihydrate (10.8 mg/1) + Phenyl salicylate (36.2 mg/1) + Sodium phosphate, monobasic, unspecified form (40.8 mg/1)TabletOralRiver's Edge Pharmaceuticals, LLC2008-12-222011-07-31Us
DarcalmaMethenamine (81.6 mg/1) + Hyoscyamine sulfate dihydrate (.12 mg/1) + Methylene blue trihydrate (10.8 mg/1) + Phenyl salicylate (36.2 mg/1) + Sodium phosphate, monobasic, unspecified form (40.8 mg/1)TabletOralKylemore Pharmaceuticals, LLC2009-12-012009-12-02Us
DarpazMethenamine (81 mg/1) + Hyoscyamine sulfate dihydrate (.12 mg/1) + Methylene blue trihydrate (10.8 mg/1) + Phenyl salicylate (32.4 mg/1) + Sodium phosphate, monobasic (40.8 mg/1)TabletOralRiver's Edge Pharmaceuticals, LLC2008-12-012011-05-31Us
Hyolev MbMethenamine (81 mg/1) + Hyoscyamine sulfate dihydrate (0.12 mg/1) + Methylene blue trihydrate (10.8 mg/1) + Phenyl salicylate (32.4 mg/1) + Sodium phosphate, monobasic, monohydrate (40.8 mg/1)TabletOralBurel Pharmaceuticals, Llc2015-06-262016-11-01Us
HyophenMethenamine (81.6 mg/1) + Benzoic Acid (9 mg/1) + Hyoscyamine sulfate dihydrate (0.12 mg/1) + Methylene blue trihydrate (10.8 mg/1) + Phenyl salicylate (36.2 mg/1)TabletOralStar Pharmaceuticals, Llc2010-09-21Not applicableUs00076 0901 01 nlmimage10 cc15e64f
Indiomin MbMethenamine (120 mg/1) + Hyoscyamine sulfate dihydrate (0.12 mg/1) + Methylene blue trihydrate (10 mg/1) + Sodium phosphate, monobasic, monohydrate (40.8 mg/1)CapsuleOralBurel Pharmaceuticals, Llc2015-09-282016-10-24Us
Me NaPhos MB Hyo 1Methenamine (81.6 mg/1) + Hyoscyamine sulfate (0.12 mg/1) + Methylene blue (10.8 mg/1) + Sodium phosphate, monobasic, monohydrate (40.8 mg/1)TabletOralMethod Pharmaceuticals2015-12-01Not applicableUs
Methenamine MandelateMethenamine mandelate (500 mg/1)TabletOralEdenbridge Pharmaceuticals Llc2009-12-15Not applicableUs
Methenamine MandelateMethenamine mandelate (1000 mg/1)Tablet, film coatedOralbryant ranch prepack2010-02-012015-03-30Us
International/Other Brands
Hexamine
Categories
UNII
J50OIX95QV
CAS number
100-97-0
Weight
Average: 140.1863
Monoisotopic: 140.106196404
Chemical Formula
C6H12N4
InChI Key
VKYKSIONXSXAKP-UHFFFAOYSA-N
InChI
InChI=1S/C6H12N4/c1-7-2-9-4-8(1)5-10(3-7)6-9/h1-6H2
IUPAC Name
1,3,5,7-tetraazatricyclo[3.3.1.1³,⁷]decane
SMILES
C1N2CN3CN1CN(C2)C3

Pharmacology

Indication

For prophylactic or suppressive treatment of frequently recurring urinary tract infections when long-term therapy is considered necessary. This drug is not used to treat infection and should only be used after appropriate eradication of infection with antimicrobial agents.

Associated Conditions
Pharmacodynamics

Ingestion of a 1-gram dose of methenamine hippurate produces antibacterial activity in the urine within 1/2 hour. Administration of 1 g twice daily produces continuous antibacterial activity in the urine.

Mechanism of action

Methenamine does not have antibacterial properties in an alkaline environment (pH≥6); however, in a more acidic environment (pH<6), methenamine is hydrolyzed to formaldehyde. (1) Formaldehyde is considered to be highly bactericidal. (1) Formaldehyde has nonspecific antibacterial activity and works by denaturing proteins and nucleic acid of bacteria. (1) Certain bacteria such as Proteus sp. can alkalize urine, inhibiting the beneficial activity of formaldehyde. (1) The key role of the salt component of the drug, for example hippuric acid, is to maintain the acidic state of the urine. (1)

Absorption

After oral administration, rapid absorption of methenamine occurs. (1)

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

When in acidic urine (pH<6), methenamine is hydrolyzed to formaldehyde which acts as an antiseptic. (1)

Route of elimination

Methenamine is primarily eliminated via the kidneys. (1)

Half life

Elimination half-life = 3-4 hours assuming normal renal function. (1)

Clearance

70-90% of a single oral dose of methenamine is excreted unchanged in the urine within 24 hours. (1)

Toxicity

Less than 3.5% of patients treated with this drug will experience minor adverse events such as upset stomach, dysuria, nausea, and rash.

Affected organisms
  • Staphylococcus saprophyticus
  • Escherichia coli
  • Enterococcus faecalis
  • Enterococcus faecium
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineThe serum concentration of 2,5-Dimethoxy-4-ethylamphetamine can be decreased when it is combined with Methenamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe serum concentration of 2,5-Dimethoxy-4-ethylthioamphetamine can be decreased when it is combined with Methenamine.
3,4-MethylenedioxyamphetamineThe serum concentration of 3,4-Methylenedioxyamphetamine can be decreased when it is combined with Methenamine.
4-Bromo-2,5-dimethoxyamphetamineThe serum concentration of 4-Bromo-2,5-dimethoxyamphetamine can be decreased when it is combined with Methenamine.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe risk or severity of adverse effects can be increased when Methenamine is combined with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
AcetazolamideThe risk or severity of adverse effects can be increased when Methenamine is combined with Acetazolamide.
Acetyl sulfisoxazoleThe risk or severity of adverse effects can be increased when Methenamine is combined with Acetyl sulfisoxazole.
AlmasilateThe therapeutic efficacy of Methenamine can be decreased when used in combination with Almasilate.
AloglutamolThe therapeutic efficacy of Methenamine can be decreased when used in combination with Aloglutamol.
AluminiumThe therapeutic efficacy of Methenamine can be decreased when used in combination with Aluminium.
Food Interactions
  • Take with food. Drink liberally.

References

General References
  1. Lo TS, Hammer KD, Zegarra M, Cho WC: Methenamine: a forgotten drug for preventing recurrent urinary tract infection in a multidrug resistance era. Expert Rev Anti Infect Ther. 2014 May;12(5):549-54. doi: 10.1586/14787210.2014.904202. Epub 2014 Apr 1. [PubMed:24689705]
External Links
Human Metabolome Database
HMDB0029598
KEGG Drug
D00393
PubChem Compound
4101
PubChem Substance
310264893
ChemSpider
3959
ChEBI
6824
ChEMBL
CHEMBL1201270
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Hexamethylenetetramine
ATC Codes
J01XX05 — Methenamine
AHFS Codes
  • 08:36.00 — Urinary Anti-infectives
FDA label
Download (1.62 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
3Not Yet RecruitingTreatmentDysuria1
4Active Not RecruitingPreventionUrinary Tract Infections, Recurrent1
4RecruitingTreatmentUrinary Tract Infections (UTIs)1
Not AvailableActive Not RecruitingPreventionCatheter-Related Infections / Urinary Tract Infections (UTIs)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral1 g
TabletOral1 g/1
TabletOral500 mg
TabletOral1000 mg/1
TabletOral500 mg/1
Tablet, film coatedOral1000 mg/1
Tablet, film coatedOral500 mg/1
CapsuleOral
TabletOral
Granule, effervescentOral
Tablet, coatedOral
Tablet, film coatedOral
Tablet, sugar coatedOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility766.0 mg/mLALOGPS
logP-1.4ALOGPS
logP0.39ChemAxon
logS0.74ALOGPS
pKa (Strongest Basic)5.88ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area12.96 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity37 m3·mol-1ChemAxon
Polarizability14.25 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Mass Spectrum (Electron Ionization)MSsplash10-0006-9300000000-e762ea01823717c4bda9
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-0006-0900000000-05c8e159897335060443
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-01ox-2900000000-86fe33e31cc8f7108c14
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-01ti-9300000000-7eb44254c8cc65c09acd
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-004i-9000000000-fd4edf8f48f9c42bca0c
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-004l-9000000000-371b89c99afba4931848
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as 1,3,5-triazinanes. These are triazinanes having three nitrogen ring atoms at the 1-, 3-, and 5- positions.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Triazinanes
Sub Class
1,3,5-triazinanes
Direct Parent
1,3,5-triazinanes
Alternative Parents
Azacyclic compounds / Aminals / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
1,3,5-triazinane / Azacycle / Aminal / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound / Aliphatic heteropolycyclic compound
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
polycyclic cage (CHEBI:6824)

Drug created on September 14, 2010 10:21 / Updated on December 12, 2018 07:18