Version October 2024
Urinary tract infection, prophylaxis for recurrent infection:
Note: May be considered in patients with bothersome, frequently recurrent cystitis despite other nonantimicrobial preventative measures. The optimal duration has not been established; up to 12 months has been studied with periodic reassessment (Ref).
Hippurate: Oral: 1 g twice daily.
Mandelate: Oral: 1 g four times daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
Note: Limited data exists in patients with kidney impairment. According to the product labeling, methenamine is contraindicated in patients with kidney impairment, although the degree of impairment is not defined. A concern is that less methenamine will be filtered or secreted into the urinary tract in patients with kidney impairment, potentially leading to decreased efficacy of the drug, although limited retrospective data suggest that some efficacy may be retained (Ref). Methenamine is relatively well tolerated, although the long-term (eg, ≥1 year) effects are not well studied (Ref).
Oral:
eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary (Ref).
eGFR <30 mL/minute/1.73 m2: Avoid use (limited data regarding safety and efficacy) (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
Oral: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Oral: Avoid use (Ref).
Peritoneal dialysis: Oral: Avoid use (Ref).
CRRT: Oral: Avoid use (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Oral: Avoid use (Ref).
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Severe impairment: Use is contraindicated.
Refer to adult dosing.
(For additional information see "Methenamine: Pediatric drug information")
Note: Urine pH should be acidic (eg, pH <5.5) for optimal efficacy.
Urinary tract infection, prophylaxis/suppression:
Methenamine hippurate:
Children 6 to 12 years: Oral: 500 to 1,000 mg twice daily
Adolescents: Oral: 1,000 mg twice daily
Methenamine mandelate:
Children <6 years: Oral: 50 to 75 mg/kg/day divided every 6 to 8 hours (Ref); maximum dose: 500 mg/dose
Children 6 to 12 years: Oral: 500 mg 4 times daily
Adolescents: Oral: 1,000 mg 4 times daily
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children and Adolescents: Use is contraindicated.
Children and Adolescents:
Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Severe impairment: Use is contraindicated.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Dermatologic: Skin rash (<4%)
Gastrointestinal: Dyspepsia (<4%), nausea (<4%)
Postmarketing:
Gastrointestinal: Abdominal distress (Harding 2022), abdominal pain (Harding 2022), diarrhea (Harding 2022), vomiting (Harding 2022)
Hepatic: Increased serum transaminases (Harding 2022)
Nervous system: Headache (Harding 2022)
Neuromuscular & skeletal: Back pain (Harding 2022)
Hypersensitivity to methenamine or any component of the formulation; severe dehydration; renal impairment; severe hepatic impairment; concurrent treatment with sulfonamides
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Disease-related concerns:
• Gout: Avoid use in patients with gout; may precipitate urate crystals in urine.
• Hepatic impairment: Use with caution in patients with hepatic impairment; reversible increases in liver function tests have occurred during therapy; periodically monitor liver function, especially in patients with hepatic impairment. Contraindicated in patients with severe impairment.
Dosage form specific issues:
• Tartrazine: Some products may contain tartrazine, which may cause allergic reactions in certain individuals.
Other warnings/precautions:
• Appropriate use: Use only when long-term therapy is indicated and infection has been eradicated by appropriate antimicrobial treatment. Should not be used to treat infections outside of the lower urinary tract. Doses of 8 g daily for 3 to 4 weeks may cause bladder irritation, painful and frequent micturition, albuminuria, and gross hematuria.
• Urinary acidification: 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); when urine acidification is contraindicated or unattainable, use is not recommended.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Hiprex: 1 g [scored; contains fd&c yellow #5 (tartrazine), saccharin sodium]
Generic: 0.5 g, 1 g
Yes
Tablets (Hiprex Oral)
1 g (per each): $2.40
Tablets (Methenamine Hippurate Oral)
1 g (per each): $2.09
Tablets (Methenamine Mandelate Oral)
0.5 g (per each): $0.89
1 g (per each): $1.67
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Restrict alkalinizing foods and medications to maintain urine pH ≤5.5.
Hippurate: Administer twice daily (morning and night).
Mandelate: Administer 4 times daily (after each meal and at bedtime).
Oral: Administer with food to minimize GI upset; patient should drink plenty of fluids to ensure adequate urine flow; administer with cranberry juice, ascorbic acid, or ammonium chloride to acidify urine; avoid intake of alkalinizing agents (sodium bicarbonate, antacids)
Urinary tract infection, prophylaxis for recurrent infection: Prophylaxis or suppression of recurrent urinary tract infections when long-term therapy is indicated and infection has been eradicated by appropriate antimicrobial treatment.
Hiprex may be confused with Mirapex
Methenamine may be confused with mesalamine, methazolAMIDE, methionine
Urex may be confused with Eurax, Serax
Urex: Brand name for methenamine [US (discontinued)], but also the brand name for furosemide [Australia, China, Turkey]
Urex [US. (discontinued)] may be confused with Eurax brand name for crotamitin [US, Canada, and multiple international markets]
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alpha-/Beta-Agonists (Indirect-Acting): Urinary Acidifying Agents may decrease the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting). Risk C: Monitor therapy
Amantadine: Urinary Acidifying Agents may decrease the serum concentration of Amantadine. Risk C: Monitor therapy
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. Management: Consider avoiding the concomitant use of medications that alkalinize the urine, such as antacids, and methenamine. Monitor for decreased therapeutic effects of methenamine if used concomitant with antacids. Risk D: Consider therapy modification
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May diminish the therapeutic effect of Methenamine. Management: Consider avoiding the concomitant use of medications that alkalinize the urine, such as carbonic anhydrase inhibitors, and methenamine. Monitor for decreased therapeutic effects of methenamine if used concomitant with a carbonic anhydrase inhibitor. Risk D: Consider therapy modification
ChlorproPAMIDE: Urinary Acidifying Agents may increase the serum concentration of ChlorproPAMIDE. Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Mecamylamine: Urinary Acidifying Agents may decrease the serum concentration of Mecamylamine. Risk C: Monitor therapy
Mycophenolate: Antibiotics may decrease serum concentrations of the active metabolite(s) of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
SulfaSALAzine: Methenamine may enhance the adverse/toxic effect of SulfaSALAzine. Specifically, the combination may result in the formation of an insoluble precipitate in the urine. Risk X: Avoid combination
Sulfonamide Antibiotics: Methenamine may enhance the adverse/toxic effect of Sulfonamide Antibiotics. Specifically, the combination may result in the formation of an insoluble precipitate in the urine. Risk X: Avoid combination
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Methenamine. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Uva Ursi: Urinary Acidifying Agents may diminish the therapeutic effect of Uva Ursi. Management: Consider avoiding use of uva ursi with agents that acidify the urine, as this may impair uva ursi efficacy. Risk D: Consider therapy modification
Foods/diets which alkalinize urine (pH >5.5) decrease therapeutic effect of methenamine.
Methenamine crosses the placenta and distributes to amniotic fluid (Allgén 1979). An increased risk of adverse fetal effects has not been observed in available studies (Furness 1975; Gordon 1972; Heinonen 1977). Methenamine use has been shown to interfere with urine estriol concentrations if measured via acid hydrolysis. Use of enzyme hydrolysis prevents this lab interference.
Methenamine is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.
Foods/diets that alkalinize urine pH >5.5 decrease activity of methenamine. Some products may contain tartrazine.
Urinalysis, periodic liver function tests
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.
Absorption: Readily from the GI tract; 10% to 30% of the drug will be hydrolyzed by gastric juices unless it is protected by an enteric coating
Distribution: Vd: 0.6 L/kg (Allgén 1979)
Metabolism: Hydrolyzed to formaldehyde and ammonia in the urine; ~10% to 25% in the liver
Half-life elimination: ~4 hours (Allgén 1979)
Time to peak: 1 to 2 hours (Allgén 1979)
Excretion: Urine (~70% to 90% as unchanged drug) within 24 hours
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