Mechanism of action: It decomposes at an acidic pH of 5.5 or less in the urine, thus producing formaldehyde, which acts locally and is toxic to most bacteria. Bacteria do not develop resistance to formaldehyde, which is an advantage of this drug. Methenamine is frequently formulated with a weak acid (for example, mandelic acid or hippuric acid) to keep the urine acidic. The urinary pH should be maintained below 6. Antacids, such as sodium bicarbonate, should be avoided
Antibacterial spectrum:
Methenamine is primarily used to reduce the frequency of UTIs. Methenamine should not be used to treat upper UTIs (for example, pyelonephritis). Urea-splitting bacteria that alkalinize the urine, such as Proteus species, are usually resistant to the action of methenamine.
Pharmacokinetics:
Methenamine is administered orally. In addition to formaldehyde, ammonium ions are produced in the bladder. Because the liver rapidly metabolizes ammonia to form urea, methenamine is contraindicated in patients with hepatic insufficiency, as ammonia can accumulate. Methenamine is distributed throughout the body fluids, but no decomposition of the drug occurs at pH 7.4. Thus, systemic toxicity does not occur, and the drug is eliminated in the urine.
Adverse effects: The major side effect of methenamine is gastrointestinal distress, albuminuria, hematuria, and rashes may develop. Methenamine is contraindicated in patients with renal insufficiency, because mandelic acid may precipitate.
Note: Sulfonamides, such as cotrimoxazole, react with formaldehyde and must not be used concomitantly with methenamine. The combination increases the risk of crystalluria and mutual antagonism