MarketMethenamine
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Methenamine

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). It is not an antibiotic, and unlike antibiotics, has no risk of bacterial resistance. Methenamine can reduce the risk of UTIs by 44 to 86% and has been found to be non-inferior to low-dose prophylactic antibiotics. It is taken by mouth. The drug is available both by prescription and at lower doses over the counter. Besides for UTI prevention, methenamine is also available in a topical form to treat hyperhidrosis.

Medical uses
Urinary tract infections Methenamine is used in the treatment and prevention of recurrent urinary tract infections (UTIs) requiring long-term therapy. It is approved and used in both adults and children at least 6years of age. As it is an antiseptic and not an antibiotic, methenamine has no risk of promoting bacterial resistance. The relative risk of symptomatic UTI was 0.24 and of bacteriuria was 0.56. This study, published in 2022, reported that methenamine (hippurate) was non-inferior to daily low-dose antibiotics for prevention of UTIs. The antibiotics used in the study included nitrofurantoin, trimethoprim, and cephalexin. Other, older studies found that methenamine was inferior to antibiotics including trimethoprim/sulfamethoxazole, trimethoprim, and nitrofurantoin in preventing or suppressing current UTIs, but these studies were of lower quality. Methenamine is not widely recommended by medical guidelines for UTI prevention as of 2022. However, this is expected to change in the near future due to the publication of the ALTAR trial and other new high-quality clinical trials. The dosing schedule of methenamine is less convenient than once-daily low-dose prophylactic antibiotics. As a result, it is not recommended for such indications. In addition, in men with persistent or recurring chronic bacterial prostatitis, prophylactic methenamine may be useful as an alternative to low-dose prophylactic antibiotics in preventing prostatitis-derived UTIs and managing associated symptoms. Prophylactic low-dose methenamine combined with an ascorbic acid (vitamin C) supplement has been reported to be effective for this purpose based on clinical experience. The skin is slightly acidic and formaldehyde can be released from methenamine in this environment. Methenamine is available both by prescription (by itself) and over the counter (in combinations). Over-the-counter formulations in combination with sodium salicylate (162.5mg) contain a lower amount of methenamine of 162mg methenamine free base per tablet compared to prescription formulations and are taken three times daily. ==Contraindications==
Contraindications
The safety of methenamine in people with renal impairment is unknown and it is considered to be contraindicated in this context. Other contraindications include severe liver disease or hepatic impairment, known hypersensitivity to methenamine or the drug formulation's components, severe dehydration, hyperphosphatemia, and use of sulfonamides. Caution is also advised in people with gout. Its safety during pregnancy is unclear and it is known to enter the placenta, amniotic fluid, and breast milk. As such, discontinuation of methenamine is recommended during breastfeeding. No teratogenic effects with methenamine in animals have been observed. Although the preceding contraindications of methenamine have been specified, they are not well-defined and may not be absolute contraindications in all cases. ==Side effects==
Side effects
Side effects of methenamine are minor and infrequent, reportedly occurring in fewer than 4% of individuals. This compound also occurs in small amounts as a contaminant in alcoholic beverages, and is chemically similar to the carcinogenic ethanol (alcohol) metabolite acetaldehyde. Because of the formaldehyde exposure with methenamine, there have been concerns about methenamine's potential carcinogenicity and the possibility that it might increase the risk of cancer, for instance bladder or stomach cancer. ==Overdose==
Overdose
Doses of methenamine much higher than usual have been clinically studied and found to produce significant toxicity. Toxic effects of such high doses included urinary tract and bladder irritation, frequent urination, strangury, and hematuria. Animal studies employing double the modern human dosage of methenamine for 6 to 12months found no adverse effects. ==Interactions==
Interactions
Concomitant use of methenamine and sulfonamides can result in insoluble methenamine salts precipitating in urine and hence is not recommended. ==Pharmacology==
Pharmacology
Pharmacodynamics Methenamine has non-specific antiseptic and antibacterial properties in acidic environments via hydrolysis into formaldehyde. Formaldehyde is an aldehyde and is highly reactive and thereby bactericidal. Elimination The drug is eliminated mainly by the kidneys. A single oral dose of methenamine is excreted 70 to 90% in urine unchanged within 24hours. The onset of action of the urinary antibacterial effects of methenamine is within 30minutes. A urinary formaldehyde concentration of 18 to 60μg/mL can be achieved with a typical therapeutic dosage of methenamine and these concentrations of formaldehyde can inhibit almost all urinary pathogens. The elimination half-life of methenamine is 2 to 6hours. ==Chemistry==
Chemistry
Methenamine, also known as 1,3,5,7-tetraazaadamantane, is a simple cyclic hydrocarbon with a cage-like structure and is similar in structure to adamantane (tricyclo[3.3.1.13,7]decane). Methenamine is usually provided medically as the hippuric acid or mandelic acid salt. Methenamine is the cation and hippuric acid or mandelic acid is the anion. ==History==
History
Methenamine was first discovered as a chemical compound in 1859. The drug was described as rapidly sterilizing and thereby restoring putrid and pus-filled urine to a normal appearance and constitution. The drug name methenamine, a contraction of the chemical or scientific name hexamethylenetetramine, was formally introduced and designated by the United States Pharmacopeia (USP) by 1925 and replaced the prior name of the drug that was being used of hexamethylenamine. The alternative drug name hexamine was introduced in the British Pharmacopoeia (BP) by 1914 to be used instead of the commercial name Urotropin. Interest in methenamine declined after the discovery of the antibiotic penicillin in 1928 and it has been described as a "forgotten drug". However, there was a surge of interest in methenamine from the 1950s to the 1980s. The topical form of methenamine for treatment of hyperhidrosis was introduced around 1965. Subsequently, there was another decline in interest in methenamine from 1980 until 2010. However, there has been another resurgence in interest in methenamine for recurrent UTI prevention since 2010 owing to increasing rates of bacterial resistance with antibiotics. Larger and higher-quality clinical trials of methenamine for UTI prevention, such as the United Kingdom ALTAR trial, have started to be published in the 2020s, and additional trials, such as the international European ImpresU trial, are also underway as of 2024. ==Society and culture==
Society and culture
Names Methenamine is the generic name of the drug and its , , and , while hexamine is its and . Brand names of methenamine include Aminoform, Antihydral, Dehydral, Formamine, Formin, Hexamine, Hiprex, Hyophen, Mandelamine, Metenamine, Phosphasal, Urelle, Urex, Uribel, Urimar, Urin DS, Urogesic Blue, Urotropin, and Ustell, among numerous others. Of 38countries that were surveyed in one study, methenamine was available in seven of them. Cost effectiveness The costs of methenamine for long-term UTI prophylaxis can be significant. However, a 2024 study found that methenamine was more cost-effective than low-dose prophylactic antibiotics for prevention of UTIs. ==Research==
Research
Methenamine might be useful in the treatment of Helicobacter pylori infections as it is activated in the acidic environment of the stomach. The drug can safely be used intravenously and might be useful in the treatment of central nervous system infections as well as certain cancers. ==See also==
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