Methenamine hippurate

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Methenamine Safety

In a 1g Methenamine Hippurate tablet, how much formaldehyde would be liberated in the body, and can this level be toxic? Is it safe to use this medication for long term treatment of recurrent UTIs considering that formaldehyde is a carcinogen?
by Shelley, 02/05/2007

Methenamine hippurate
Methenamine hippurate (Hip-Rex )
(meh- THEEN-ah-meen)
Pregnancy Category: C Hip-Rex Hiprex Urex (Rx)
Methenamine mandelate
Methenamine mandelate (Mandelamine)
(meh- THEEN-ah-meen)
Pregnancy Category: C Mandelamine (Rx)

Classification: Urinary tract anti-infective

Action/Kinetics: Converted in an acid medium into ammonia and formaldehyde (the active principle), which denatures protein. Formaldehyde levels in the urine may be bacteriostatic or bactericidal, depending on the pH; it is most effective when the urine has a pH value of 5.5 or less, which is maintained by using the hippurate or mandelate salt. Readily absorbed from GI tract, but up to 60% may be hydrolyzed by gastric acid if tablets are not enteric-coated. To be effective, urinary formaldehyde concentration must be greater than 25 mcg/mL. Peak levels of formaldehyde: 2 hr if using hippurate and 3-8 hr if using mandelate (if urinary pH is 5.5 or less) t 1/2: 3-6 hr. Seventy to 90% of drug and metabolites excreted in urine within 24 hr.

Uses: Acute, chronic, and recurrent UTIs by susceptible organisms, especially gram-negative organisms including Escherichia coli. As a prophylactic before urinary tract instrumentation. Never used as sole agent in the treatment of acute infections.

Contraindications: Renal insufficiency, severe liver damage, severe dehydration. Concurrent use of sulfonamides as an insoluble precipitate may form with formaldehyde.

Special Concerns: Use with caution in gout (methenamine may cause urate crystals to precipitate in the urine).

Side Effects: GI: N&V, diarrhea, anorexia, cramps, stomatitis. GU: Hematuria, albuminuria, crystalluria, dysuria, urinary frequency or urgency, bladder irritation. Dermatologic: Skin rashes, urticaria, pruritus, erythematous eruptions. Other: Headache, dyspnea, edema, lipoid pneumonitis.

Laboratory Test Alterations: False + urinary glucose with Benedict's solution. Drug interferes with determination of urinary catecholamines and estriol levels by acid hydrolysis technique (enzymatic techniques not affected). False + catecholamines, hydroxycorticosteroids, vanillylmandelic acid; false - 5-hydroxyindoleacetic acid.

Overdose Management: Treatment: Absorption following overdose may be minimized by inducing vomiting or by gastric lavage, followed by activated charcoal. Fluids should be forced.

Drug Interactions: Acetazolamide / Methenamine effect R/T inhibition of conversion to formaldehyde Sodium bicarbonate / Methenamine effect R/T inhibition of conversion to formaldehyde Sulfonamides / Chance of sulfonamide crystalluria R/T acid urine produced by methenamine Thiazide diuretics / Methenamine effect R/T urine alkalinity produced by thiazides

How Supplied: Methenanamine hippurate: Tablet: 1 g Methenamine mandelate: Tablet: 0.5 g, 1 g; Suspension: 0.5 g/5 mL

Hippurate: Adults and children over 12 years: 1 g b.i.d. in the morning and evening; children, 6-12 years: 0.5 g b.i.d.
?Oral Suspension, Enteric-Coated Tablets
Mandelate: Adults: 1 g q.i.d. after meals and at bedtime; children 6-12 years: 0.5 g q.i.d.; children under 6 years: 0.25 g/13.6 kg q.i.d.

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