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Methenamine: Drug information

Methenamine: Drug information
(For additional information see "Methenamine: Patient drug information" and see "Methenamine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Hiprex
Pharmacologic Category
  • Antibiotic, Miscellaneous
Dosing: Adult
Urinary tract infection, prophylaxis/suppression

Urinary tract infection, prophylaxis/suppression: Oral:

Hippurate: 1,000 mg twice daily

Mandelate: 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.

Dosing: Kidney Impairment: Adult

Note: Limited data is available in patients with renal impairment (Lee 2002).

Mild to severe impairment: Use is contraindicated.

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Severe impairment: Use is contraindicated.

Dosing: Pediatric

(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

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 (Red Book [AAP 2003]); 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.

Dosing: Kidney Impairment: Pediatric

Children and Adolescents: Use is contraindicated.

Dosing: Hepatic Impairment: Pediatric

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.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

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

Generic Equivalent Available: US

Yes

Administration: Adult

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).

Administration: Pediatric

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)

Use: Labeled Indications

Urinary tract infection, prophylaxis/suppression: Prophylaxis or suppression of recurrent urinary tract infections when long-term therapy is indicated and infection has been eradicated by appropriate antimicrobial treatment

Medication Safety Issues
Sound-alike/look-alike issues:

Hiprex may be confused with Mirapex

Methenamine may be confused with mesalamine, methazolAMIDE, methionine

Urex may be confused with Eurax, Serax

International issues:

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]

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Large doses (higher than recommended) have resulted in bladder irritation, frequent/painful micturition, albuminuria, and hematuria.

<4%:

Dermatologic: Pruritus, skin rash

Gastrointestinal: Dyspepsia, nausea, vomiting

<1%, postmarketing, and/or case reports: Increased serum ALT (reversible), increased serum AST (reversible)

Contraindications

Hypersensitivity to methenamine or any component of the formulation; severe dehydration; renal impairment; severe hepatic impairment; concurrent treatment with sulfonamides

Warnings/Precautions

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.

Metabolism/Transport Effects

None known.

Drug Interactions

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 Lexicomp 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

Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. 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

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

Food Interactions

Foods/diets which alkalinize urine (pH >5.5) decrease therapeutic effect of methenamine.

Pregnancy Considerations

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.

Breastfeeding Considerations

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.

Dietary Considerations

Foods/diets that alkalinize urine pH >5.5 decrease activity of methenamine. Some products may contain tartrazine.

Monitoring Parameters

Urinalysis, periodic liver function tests

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.

Pharmacokinetics

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

Pricing: US

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 - $2.37

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.

Brand Names: International
  • Antihydral (CH, LU);
  • Haiprex (DK, IS);
  • Hexamandin (PL);
  • Hipeksal (FI);
  • Hiprex (AE, AT, AU, BB, BF, BJ, BM, BS, BZ, CI, CR, DO, ET, FI, GB, GH, GM, GN, GT, GY, HN, JM, KE, LR, MA, ML, MR, MU, MW, MX, MY, NE, NG, NO, NZ, OM, PA, PH, SC, SD, SE, SL, SN, SR, SV, TN, TT, TZ, UG, ZA, ZM, ZW);
  • Mandehexan (PL);
  • Mandelamine (PL);
  • Pedipur (PL);
  • Reflux (NL);
  • Stoppot (PL);
  • Urotractan (DE);
  • Xcyst (NL)


For country code abbreviations (show table)
  1. Allgén 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):287-293. [PubMed 484222]
  2. American Academy of Pediatrics (AAP). In: Pickering LK, Baker CJ, Overtuf GD, Prober DC, eds. Red Book: 2003 Report of the Committee on Infectious Diseases. 26th ed. American Academy of Pediatrics; 2003.
  3. Furness ET, McDonald PJ, Beasley NV. Urinary Antiseptics in Asymptomatic Bacteriuria of Pregnancy. N Z Med J. 1975;81(539):417-419. [PubMed 1099490]
  4. Gordon SF. Asymptomatic Bacteriuria of Pregnancy. Clinical Medicine. 1972:22-24.
  5. Heinonen OP, Slone D, Shapiro S. Birth Defects and Drugs in Pregnancy. Publishing Sciences Group Inc; 1977.
  6. Hiprex (methenamine) [prescribing information]. Parsippany, NJ: Validus Pharmaceuticals LLC; July 2021.
  7. Hooton TM, Bradley SF, Cardenas DD, et al; Infectious Diseases Society of America. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(5):625-663. [PubMed 20175247]
  8. Lee B, Bhuta T, Craig J, Simpson J. Methenamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev. 2002;(1):CD003265. doi:10.1002/14651858.CD003265 [PubMed 11869659]
  9. Methenamine mandelate [prescribing information]. Congers, NY: Chartwell Rx LLC; September 2021.
  10. Urex tablets (methenamine) [prescribing information]. Wytheville VA: Vatring Pharmaceuticals Inc; December 2006.
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