Methenamine

and

Methenamine Salts

Pronunciation: (me-THE-na-meen and me-THE-na-meen salts)
Class: Anti-infective agent Methenamine Hippurate Methenamine Mandelate

Trade Names

Hiprex
- Tablets 1 g (as hippurate)

Methenamine Mandelate
- Tablets 0.5 g
- Tablets 1 g

Urex
- Tablets 1 g (as hippurate)

Dehydral (Canada)

Pharmacology

In acidic urine, methenamine is hydrolyzed to ammonia and formaldehyde, which is bactericidal to certain bacteria in urine. Acid salts (mandelate and hippurate) have some nonspecific bacteriostatic activity and help to maintain low urine pH.

Pharmacokinetics

Absorption

Readily absorbed from the GI tract.

Distribution

Methenamine is freely distributed to body tissues and fluids.

Metabolism

Methenamine is hydrolyzed in acidic urine (pH at least 5.5) to ammonia and formaldehyde.

Elimination

Methenamine is eliminated renally via glomerular filtration and tubular secretion.

Onset

30 min (methenamine hippurate).

Special Populations

Renal Function Impairment

No pharmacokinetic data available. Contraindicated in patients with renal insufficiency.

Hepatic Function Impairment

No pharmacokinetic data available. Contraindicated in patients with severe hepatic disease.

Indications and Usage

Methenamine hippurate

For prophylactic or suppressive treatment of frequently recurring UTIs when long-term therapy is considered necessary.

Methenamine mandelate

Suppression or elimination of bacteriuria associated with pyelonephritis, cystitis, and other chronic UTIs; treatment of infected residual urine, sometimes accompanying neurologic disease.

Contraindications

Renal insufficiency; severe dehydration; severe hepatic insufficiency; hypersensitivity to any component of the product; acute UTIs involving renal parenchyma; concomitant sulfonamide therapy (methenamine hippurate).

Dosage and Administration

Methenamine Hippurate
Adults and Children 13 y of age and older

PO 1 g twice daily (morning and night).

Children 6 to 12 y of age

PO 500 mg to 1 g twice daily (morning and night).

Methenamine Mandelate
Adults and Children 13 y of age and older

PO 4 g daily given as 1 g after each meal and at bedtime.

Children 6 to 12 y of age

PO 2 g daily given as 500 mg after each meal and at bedtime.

Children 5 y of age and younger

PO 250 mg for every 30 lb of body weight, 4 times daily.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

Food

The antibacterial activity of methenamine is greater in acid urine; therefore, restriction of alkalinizing foods and medications (eg, sodium bicarbonate) is desirable.

Sulfonamides

May increase the risk of crystalluria. Avoid coadministration of sulfonamides and methenamine.

Urine alkalizers (acetazolamide, sodium bicarbonate, sodium carbonate)

Prevents hydrolysis of methenamine to formaldehyde with possible decrease in antimicrobial action. If coadministration cannot be avoided and an interaction is suspected (ie, suboptimal antimicrobial response), consider discontinuing the urinary alkalinizers or selecting an alternative antibiotic (eg, nitrofurantoin).

Laboratory Test Interactions

Methenamine may interfere with laboratory urine determinations of 17-hydroxycorticosteroids, catecholamines, and vanillylmandelic acid (false increases); and 5-hydroxyindoleacetic acid (false decrease). If taken during pregnancy, it can interfere with laboratory tests for urine estriol (false decrease) when acid hydrolysis procedure is used; use enzymatic hydrolysis procedure.

Adverse Reactions

Dermatologic

Rash (less than 3.5%); pruritus (rare).

GI

Nausea, upset stomach, vomiting (less than 3.5%).

Genitourinary

Dysuria (less than 3.5%); painful or difficult urination; microscopic and, rarely, gross hematuria.

Precautions

Monitor

Monitor liver function studies periodically. Monitor efficacy of therapy with repeat urine cultures. Urinary pH monitoring is required to ensure an acidic urinary pH (below 5.5).

Pregnancy

Category C .

Lactation

Excreted.

Elderly

Dose selection should be cautious, usually reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Renal Function

Contraindicated in patients with renal insufficiency.

Hepatic Function

Contraindicated in patients with severe hepatic disease.

Tartrazine Sensitivity

Some products contain tartrazine, which may cause rash or bronchial asthma in susceptible patients.

Acid urine

Care should be taken to maintain an acid pH of the urine, especially when treating infections due to urea-splitting organisms such as Proteus species and strains of Pseudomonas species. When urine acidification is contraindicated or unattainable (as with some urea-splitting bacteria), the drug is not recommended.

Dysuria

Dysuria may occur (usually at higher than recommended dosage). This can be controlled by reducing the dosage and the acidification.

Drug-resistant bacteria

Prescribing methenamine in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of development of drug-resistant bacteria.

Gout

May cause precipitation of urate crystals in urine. Avoid use.

Large doses

Large doses of methenamine (8 g daily for 3 to 4 wk) have caused bladder irritation, painful and frequent micturition, albuminuria, and gross hematuria.

Patient Information

Explain significance of adequate hydration.
Tell patient to report the following symptoms to health care provider: headache, painful urination, skin rash, swelling, or severe stomach upset.
Instruct patient to avoid use of milk products and antacids while taking drug to help keep urine acidic and allow drug to work better. Instruct patient to take vitamin C and drink cranberry or prune juice to acidify urine.
Caution patient not to self-medicate with OTC medications containing sodium bicarbonate or sodium carbonate.
Teach patient how to read dipstick tests for urine pH and specific gravity and to report to health care provider if required values are not attained.