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Pronunciation
(meth EN a meen)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Prophylaxis or suppression of recurrent urinary tract infections; urinary tract discomfort secondary to hypermotility
Pregnancy Risk Factor
C (methenamine mandelate)
Pregnancy Considerations
Because animal reproduction studies were not conducted, methenamine mandelate is classified pregnancy category C. Methenamine hippurate did not cause adverse fetal effects in animals. Methenamine crosses the placenta and distributes to amniotic fluid. Adverse fetal effects were not observed in two human trials. Methenamine use has been shown to interfere with urine estriol concentrations if measured via acid hydrolysis. Use of enzyme hydrolysis prevents this lab interference.
Lactation
Enters breast milk
Breast-Feeding Considerations
Small amounts of methenamine are secreted in human milk.
Contraindications
Hypersensitivity to methenamine or any component of the formulation; severe dehydration, renal insufficiency, severe hepatic insufficiency; concurrent treatment with sulfonamides
Warnings/Precautions
Concerns related to adverse effects:
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Gout: Use with caution in patients with gout.
• Hepatic impairment: Use with caution in patients with hepatic impairment; reversible increases in LFTs have occurred during therapy especially in patients with hepatic dysfunction. Contraindicated in patients with severe impairment.
Special populations:
• Elderly: Use with caution in the elderly.
Dosage form specific issues:
• Tartrazine: Hiprex® contains tartrazine dye, which may cause allergic reactions in certain individuals.
Other warnings/precautions:
• Appropriate use: Should not be used to treat infections outside of the lower urinary tract; doses of 8 g/day for 3-4 weeks may cause bladder irritation. Use care to maintain an acid pH of the urine, especially when treating infections due to urea splitting organisms (eg, Proteus and strains of Pseudomonas)
Adverse Reactions
<4%:
Dermatologic: Pruritus, rash
Gastrointestinal: Dyspepsia, nausea, vomiting
Hepatic: ALT increased (reversible; rare), AST increased (reversible; rare)
Note: Large doses (higher than recommended) have resulted in bladder irritation, frequent/painful micturition, albuminuria, and hematuria.
Metabolism/Transport Effects
None known.
Drug Interactions
Amphetamines: Methenamine may decrease the serum concentration of Amphetamines. This effect is likely due to an enhanced excretion of amphetamines in the urine. Risk C: Monitor therapy
Antacids: May diminish the therapeutic effect of Methenamine. Risk D: Consider therapy modification
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Carbonic Anhydrase Inhibitors: May diminish the therapeutic effect of Methenamine. Management: Consider avoiding this combination. Monitor for decreased therapeutic effects of methenamine if used concomitant with a carbonic anhydrase inhibitor. Exceptions: Brinzolamide; Dorzolamide. Risk D: Consider therapy modification
Sulfonamide Derivatives: Methenamine may enhance the adverse/toxic effect of Sulfonamide Derivatives. Specifically, the combination may result in the formation of an insoluble precipitate in the urine. Risk X: Avoid combination
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food: Foods/diets which alkalinize urine (pH >5.5) decrease therapeutic effect of methenamine.
Storage
Store at room temperature of 15°C to 30°C (59°F to 86°F). Protect from light.
Mechanism of Action
Methenamine is hydrolyzed to formaldehyde and ammonia in acidic urine; formaldehyde has nonspecific bactericidal action. Other components, hippuric acid or mandelic acid, aid in maintaining urine acidity and may aid in suppressing bacteria.
Pharmacodynamics/Kinetics
Absorption: Readily
Metabolism: Gastric juices: Hydrolyze 10% to 30% unless protected via enteric coating; Hepatic: ~10% to 25%
Half-life elimination: 3-6 hours
Excretion: Urine (90% as unchanged drug) within 24 hours
Dosage
Oral:
Children:
>2-6 years: Mandelate: 50-75 mg/kg/day in 3-4 doses or 0.25 g/30 lb 4 times/day
6-12 years:
Hippurate: 0.5-1 g twice daily
Mandelate: 50-75 mg/kg/day in 3-4 doses or 0.5 g 4 times/day
>12 years and Adults:
Hippurate: 1 g twice daily
Mandelate: 1 g 4 times/day after meals and at bedtime
Dosing adjustment/comments in renal impairment: Clcr <50 mL/minute: Avoid use
Administration: Oral
Administer around-the-clock to promote less variation in effect.
Monitoring Parameters
Urinalysis, periodic liver function tests
Test Interactions
Increased urinary catecholamines, 17-hydroxycorticosteroid and vanillylmandelic acid (VMA) levels; decreased urinary 5-hydroxyindoleacetic acid (5HIAA) and estriol levels
Dietary Considerations
Foods/diets which alkalinize urine pH >5.5 decrease activity of methenamine; cranberry juice can be used to acidify urine and increase activity of methenamine. Hiprex® contains tartrazine dye.
Patient Education
Maintain adequate hydration unless instructed to restrict fluid intake. Avoid milk or alkalizing medications. May cause nausea, vomiting, or GI upset. Report pain on urination or blood in urine, skin rash, or if condition does not improve.
Geriatric Considerations
Methenamine has little, if any, role in the treatment or prevention of infections in patients with indwelling urinary (Foley) catheters. Furthermore, in noncatheterized patients, more effective antibiotics are available for the prevention or treatment of urinary tract infections. The influence of decreased renal function on the pharmacologic effects of methenamine results are unknown.
Additional Information
Should not be used to treat infections outside of the lower urinary tract. Methenamine has little, if any, role in the treatment or prevention of infections in patients with indwelling urinary (Foley) catheters. Furthermore, in noncatheterized patients, more effective antibiotics are available for the prevention or treatment of urinary tract infections.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess urinalysis (indicates resolution of infection).
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral, as hippurate: 1 g
Hiprex®: 1 g [scored; contains tartrazine]
Tablet, oral, as mandelate: 500 mg, 1 g
Pricing: U.S. (www.drugstore.com)
Tablets (Hiprex)
1 g (20): $53.99
Tablets (Methenamine Hippurate)
1 g (100): $185.99
References
Allgen LG, Holmberg G, Persson B, et al, “Biological Fate of Methenamine in Man. Absorption, Renal Excretion and Passage to Umbilical Cord Blood, Amniotic Fluid and Breast Milk,” Acta Obstet Gynecol Scand, 1979, 58(3):287-93.
Carlstrom K and Lunell NO, “Interference of Antiseptics Containing Hexamethylene Tetraamine (Hiprex®) With the Estimation of Urinary Oestriol Excretion During Pregnancy,” Acta Obstet Gynecol Scand, 1975, 54(4):387-8.
Kivinen S and Tuimala R, “Decreased Urinary Oestriol Concentrations in Pregnant Women During Hexamine Hippurate Treatment,” Br Med J, 1977, 2(6088):682.
“Safety of Antimicrobial Drugs in Pregnancy,” Med Lett Drugs Ther, 1987, 29(743):61-3.
Vainrub B and Musher DM, “Lack of Effect of Methenamine in Suppression of, or Prophylaxis Against, Chronic Urinary Tract Infection,” Antimicrob Agents Chemother, 1977, 12:625-9.
International Brand Names
Lexi-Comp.com
Last full review/revision October 2011
Content last modified October 2011
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