Drug General Information (ID: DDI216RKNM)
Drug Name			Metolazone		Drug Info		Methenamine		Drug Info
Drug Type		Small molecule				Small molecule
Therapeutic Class		Antihypertensive Agents				Urinary Antispasmodics
Structure

Mechanism of Metolazone-Methenamine Interaction (Severity Level: Moderate)
Altered urine pH Click to Show/Hide Mechanism Graph
Drug Name		Metolazone				Methenamine
Mechanism		Urine pH sensitive				Urine alkalinizer
Key Mechanism Factor 1
		Factor Name		Urine pH
		Factor Description		The normal range of urine pH is between 4.5 and 8, depending mainly on the hydrogen ion concentration. Changes in urine pH may significantly affect drug reabsorption and excretion.
Mechanism Description		Altered elimination of Metolazone caused by Methenamine mediated altered urine pH

Recommended Action
Management		Concomitant use of methenamine-containing preparations with thiazide diuretics, carbonic anhydrase inhibitors, or large doses of antacids should be avoided if possible. Otherwise, frequent urine pH testing may be considered. Some methenamine products may be used with antacids if dosing times are separated by at least one hour. Consult the manufacturer's product labeling for specific recommendations.

References
1	Kevorkian C, Merritt J, Ilstrup D "Methenamine mandelate with acidification: an effective urinary antiseptic in patients with neurogenic bladder." Mayo Clin Proc 59 (1984): 523. [PMID: 6379319]
2	Musher D, Griffith D "Generation of formaldehyde from methenamine: effect of pH and concentration, and antibacterial effect." Antimicrob Agents Chemother 6 (1974): 708-11. [PMID: 4451344]
3	Product Information. Hiprex (methenamine). Hoechst Marion-Roussel Inc, Kansas City, MO.
4	Product Information. Hyophen (benzoic acid/hyoscy/methen/mblue/phenylsal). BioComp Pharma, San Antonio, TX.
5	Sand TE, Jacobsen S "Effect of urine pH and flow on renal clearance of methotrexate." Eur J Clin Pharmacol 19 (1981): 453-6. [PMID: 7250179]