Methenamine Mandelate

Antibacterial.100 101 102

General

• Acidic urine is essential for antibacterial activity; maximum efficacy occurs when urine pH is ≤5.5.102 Restrict alkalinizing food and medication;101 102 use supplemental acidification if needed.100 101 102 a

Administration

Oral Administration

Administer orally.100 101 102

Dosage

Available as methenamine hippurate and methenamine mandelate; dosage expressed in terms of the salt.100 101 102

Pediatric Patients

Children <6 years of age: Dosage not established.a

Children 6–12 years of age: 500 mg to 1 g twice daily (morning and night).100 101

Children >12 years of age: 1 g twice daily (morning and night).100 101

Children <6 years of age: 18.4 mg/kg 4 times daily, (after meals and at bedtime).102

Children 6–12 years of age: 500 mg 4 times daily (after meals and at bedtime).102

Children >12 years of age: 1 g 4 times daily (after meals and at bedtime).102

Alternatively, some clinicians recommend 50 mg/kg daily in 3 divided doses for children.a

Adults

1 g twice daily (morning and night).100 101

1 g 4 times daily (after meals and at bedtime).102

Special Populations

No special population dosage recommendations at this time.100 101 102

Contraindications

• Known hypersensitivity to the drug.102

• Renal insufficiency.100 101 102

• Severe hepatic insufficiency100 101 or severe dehydration.100 101

Warnings/Precautions

Warnings

Large doses (8 g daily for 3–4 weeks) have caused bladder irritation, painful and frequent micturition, albuminuria, and gross hematuria.100 101

Dysuria may be controlled by reducing dosage and/or reducing urine acidification.102

Patients with preexisting hepatic insufficiency may have adverse effects from the small amounts of ammonia and formaldehyde that are produced following administration of methenamine.100 Acute hepatic failure may occur in some patients.100

Transient elevations in serum AST and ALT concentrations have occurred in patients receiving methenamine hippurate.100 101

Perform periodic liver function tests in patients receiving methenamine hippurate, especially in those with hepatic impairment.100 101 (See Hepatic Impairment under Cautions.)

Sensitivity Reactions

Hiprex tablets contain tartrazine (FD&C yellow No. 5), which may cause allergic reactions, including bronchial asthma, in susceptible individuals.101 Incidence of tartrazine sensitivity is low, but it frequently occurs in patients who are sensitive to aspirin.101

General Precautions

Ensure that urine is maintained at an acidic pH during treatment, especially when causative organisms are urea-splitting strains of Proteus or Pseudomonas.100 101 (See Dosage and Administration.)

Manufacturer of methenamine mandelate states the drug is not recommended if urine acidification is contraindicated or unattainable (e.g., when some urea-splitting bacteria are present).102

To reduce development of drug-resistant bacteria and maintain effectiveness of methenamine and other antibacterials, use only to prevent infections proven or strongly suspected to be caused by susceptible bacteria.101

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.101 In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.101

Specific Populations

Category C.100 102

One manufacturer of methenamine hippurate states that safety during the last trimester is suggested, but not definitely proven.101

Effects of methenamine during labor and delivery are unknown and there are no recognized uses for the drug during labor or delivery.100

Distributed into milk; discontinue nursing or the drug.100

Has been used in children without unusual toxicity.100

Insufficient experience in patients ≥65 years of age to determine whether they respond differently than younger adults; clinical experience has not identified differences.101

Select dosage with caution, usually starting at the low end of the dosage range, because of possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.101

Perform periodic liver function tests.100 101

Methenamine hippurate is contraindicated in those with severe hepatic insufficiency.100 101

Common Adverse Effects

GI disturbances (nausea, vomiting, diarrhea, abdominal cramps, anorexia), pruritus, rash, dysuria.100 101 102 a

Absorption

Bioavailability

Readily absorbed from the GI tract.a About 10–30% of oral dose is hydrolyzed by gastric acidity to formaldehyde and ammonia.a Enteric coating of methenamine mandelate tablets reduces hydrolysis in the GI tract and rate of absorption.a

Plasma Concentrations

Following oral administration of a usual single dose to healthy fasting adults, concentrations of methenamine and formaldehyde in plasma are generally very low and antibacterial activity in plasma is negligible.a

Distribution

Extent

Crosses the placenta.100

Distributed into milk.100

Elimination

Elimination Route

Within 24 hours, ≥70–90% of a single oral dose is excreted intact in the urine by glomerular filtration and tubular secretion.a When urine is acidic, methenamine is hydrolyzed to formaldehyde and ammonia; maximum hydrolysis occurs when urine pH is ≤5.5.a

Mandelic acid (mandelate) and hippuric acid (hippurate) are excreted in urine by glomerular filtration and tubular excretion.101 102

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name