METHENAMINE MANDELATE- methenamine mandelate_tablet, film coated

Methenamine mandelate is readily absorbed but remains essentially inactive until it is excreted by the kidneys and concentrated in the urine. An acid urine is essential for antibacterial action, with maximum efficacy occurring at pH 5.5 or less. In an acid urine, mandelic acid exerts its antibacterial action and also contributes to the acidification of the urine. Mandelic acid is excreted both by glomerular filtration and tubular excretion. The methenamine component is hydrolyzed in acid urine to ammonia and to the bactericidal agent formaldehyde. Proportionally less formaldehyde is released as urinary pH approaches 6.0 and insufficient quantities are released above this level for therapeutic response. There is equally effective antibacterial activity against both gram-positive and gram-negative organisms, since the antibacterial action of mandelic acid and formaldehyde is nonspecific. There are reports that methenamine mandelate is ineffective in some infections with Proteus vulgaris Pseudomonas aeruginosa A aerogenes

Methenamine mandelate is indicated for the suppression or elimination of bacteriuria associated with pyelonephritis, cystitis, and other chronic urinary tract infections; also those neurologic diseases leading to an infected residual urine. When used as recommended, methenamine mandelate is particularly suitable for long-term therapy because of its safety and because resistance to the nonspecific bactericidal action of formaldehyde does not develop. Pathogens resistant to other antibacterial agents may respond to methenamine mandelate because of the nonspecific effect of formaldehyde formed in an acid urine. Prophylactic Use Rationale: Therapeutic Use Rationale:

The average adult dose is 4 g a day given as 1 g tablet after each meal and at bedtime. Children 6 to 12 years of age should receive half the adult dose; one-half tablet 4 times a day.

Gastrointestinal disturbances (nausea, stomach upset), generalized skin rash, dysuria, painful or difficult urination may occur occasionally with the use of methenamine preparations. Microscopic and rarely, gross hematuria have been described.

Methenamine mandelate tablets are contraindicated in patients with renal insufficiency, severe hepatic disease severe dehydration, and in patients who have exhibited hypersensitivity to any components of this product.

Methenamine is excreted in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

WARNINGS
Methenamine mandelate should be avoided in patients with gout because it may precipitate urate crystals in their urine. A similar situation may arise in patients with a predisposition to the formation of uric acid stones. Methenamine preparations should not be given to patients taking sulfonamides because some sulfonamides may form an insoluble precipitate with formaldehyde in the urine.
CARCINOGENESIS and MUTAGENESIS
Methenamine mandelate has not been evaluated for carcinogenicity or mutagenicity. Methenamine was evaluated for mutagenicity in the Ames Salmonella/mammalian microsome test. Five strains of Salmonella typhimurium (TA98, TA100, TA1535, TA1537 and TA1538) and a strain of Escherichia coli (WP2uvrA) were used. At a dose of 10,000 µg/plate methenamine showed mutagenic activity in Salmonella typhimurium TA98 and TA100 by metabolic activation and also showed mutagenic activity in TA98 without microsomal activation. In one large study, no evidence of carcinogenicity was found following long-term oral administration of methenamine 1.25 g/kg/day to rats (104 weeks) and mice (60 weeks).
Teratogenic Effects.
Animal reproduction studies have not been conducted with methenamine mandelate. It is also not known whether methenamine mandelate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Since methenamine is known to cross the placental barrier, methenamine mandelate should be given to a pregnant woman only if the potential benefit outweighs the risk.
OVERDOSAGE
Minimize absorption by inducing vomiting or by gastric lavage followed by administration of activated charcoal. Administer orally fluids and alkalinize with sodium bicarbonate.

Seton Pharmaceuticals

METHENAMINE MANDELATE- methenamine mandelate_tablet, film coated Product manual source documgent