Class: Urinary Anti-infectives
Note: This monograph also contains information on Methenamine, Methenamine Hippurate
VA Class: AM550
CAS Number: 100-97-0
Brands: Hiprex, Mandelamine, Urex
Introduction
Antibacterial.100 101 102
Uses for Methenamine Mandelate
Urinary Tract Infections (UTIs)
Prophylaxis or suppression of recurrent UTIs (bacteriuria), especially when long-term therapy is considered necessary.100 101 102
Use only after UTI has been eradicated by other appropriate anti-infectives.100 101
Not effective in systemic bacterial infections and has no effect on bacteria in blood or tissues outside the urinary tract.a Do not use alone in the treatment of acute parenchymal infections causing systemic symptoms (e.g., chills, fever).100 102
Monitor efficacy by periodic urine cultures.100 101
Antibacterial effects are maximal when urine pH is ≤5.5.102 Monitor urinary pH during therapy; use supplementary acidification, if required.101 102 Supplementary acidification may be achieved by dietary regulation and/or concomitant administration of acidifying agents (e.g., ammonium chloride, ascorbic acid, methionine).a This is particularly important when the causative organisms are urea-splitting strains of Proteus or Pseudomonas which increase urinary pH.100 101
Methenamine Mandelate Dosage and Administration
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
Prophylaxis or Suppression of Urinary Tract Infections (UTIs)
Methenamine Hippurate
Oral
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
Methenamine Mandelate
Oral
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
Prophylaxis or Suppression of Urinary Tract Infections (UTIs)
Methenamine Hippurate
Oral
1 g twice daily (morning and night).100 101
Methenamine Mandelate
Oral
1 g 4 times daily (after meals and at bedtime).102
Special Populations
No special population dosage recommendations at this time.100 101 102
Cautions for Methenamine Mandelate
Contraindications
Known hypersensitivity to the drug.102
Renal insufficiency.100 101 102
Severe hepatic insufficiency100 101 or severe dehydration.100 101
Warnings/Precautions
Warnings
Dysuria
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
Hepatic Effects
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
Tartrazine Sensitivity
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
Acidic Urine
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
Selection and Use of Anti-infectives
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
Pregnancy
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
Lactation
Distributed into milk; discontinue nursing or the drug.100
Pediatric Use
Has been used in children without unusual toxicity.100
Geriatric Use
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
Hepatic Impairment
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
Interactions for Methenamine Mandelate
Specific Drugs and Laboratory Tests
Drug or Test | Interaction | Comments |
|---|---|---|
Sulfonamides | Insoluble precipitate forms in urine between formaldehyde and some sulfonamides (e.g., sulfamethizole, sulfathiazole [not commercially available in the US])100 101 102 | Avoid concomitant use100 101 102 |
Test for 17-hydroxycorticosteroid | Formaldehyde in urine causes falsely elevated concentrations when Porter-Silber method is used102 | |
Test for 5-hydroxyindoleacetic acid (5HIAA) | Formaldehyde in urine causes falsely decreased concentrations when nitrosonaphthol methods are used102 | |
Test for urinary catecholamines and vanillylmandelic acid (VMA) | Formaldehyde in urine causes erroneously high results when fluorometric procedures are used102 | |
Test for urine estriol | Formaldehyde in urine causes falsely decreased urine estriol concentrations when acid hydrolysis techniques are used101 102 | Enzymatic hydrolysis technique unaffected101 102 |
Methenamine Mandelate Pharmacokinetics
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
Stability
Storage
Oral
Tablets
15–30°C100 101 102 in tight, light resistant containers.102
Actions and SpectrumActions
Synthetic antibacterial agent chemically unrelated to other currently available anti-infectives.a
Antibacterial effect of methenamine hippurate or methenamine mandelate depends on conversion of methenamine to formaldehyde in an acid medium (acidic urine).a
Formaldehyde is a nonspecific antibacterial agent which is usually bactericidal in action.a The acid portions of methenamine salts (hippuric acid, mandelic acid) have some nonspecific antibacterial activity and may enhance the liberation of formaldehyde from methenamine in vivo by maintaining urinary acidity.a
Formaldehyde is active against both gram-positive and gram-negative bacteria including Enterobacter, Escherichia coli, Klebsiella, Proteus, Pseudomonas aeruginosa, Staphylococcus aureus, S. epidermidis, and Enterococcus faecalis (formerly Streptococcus faecalis).a
Because formaldehyde, hippuric acid, and mandelic acid have nonspecific antibacterial activity, resistance does not usually develop during prolonged therapy with methenamine hippurate or methenamine mandelate.a
Advice to Patients
Advise patients that antibacterials (including methenamine hippurate and methenamine mandelate) should only be used for bacterial infections and not used to treat viral infections (e.g., the common cold).101
Importance of completing full course of therapy, even if feeling better after a few days.101
Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with methenamine or other antibacterials in the future.101
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs or laboratory tests.100 101 102
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.100 101 102
Importance of informing patients of other important precautionary information.100 101 102 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets | 1 g* | Hiprex (with povidone and tartrazine; scored) | Sanofi-Aventis |
Methenamine Hippurate Tablets | Corepharma | |||
Urex (with povidone; scored) | Vatring |
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 500 mg | Mandelamine Hafgrams (with povidone and polyethylene glycol) | Warner Chilcott |
1 g | Mandelamine (with povidone and polyethylene glycol) | Warner Chilcott |
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 04/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Hiprex 1GM Tablets (SANOFI-AVENTIS U.S.): 20/$49.99 or 60/$139.97
Methenamine Hippurate 1GM Tablets (COREPHARMA LLC): 100/$185.99 or 300/$535.99
Urex 1GM Tablets (VATRING PHARMACEUTICALS): 30/$68.99 or 90/$199.97
Disclaimer
This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions January 01, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References
100. Vatring. Urex (methenamine hippurate) prescribing information. Wytheville, VA; 2004 Aug.
101. Sanofi-Aventis. Hiprex (methenamine hippurate) prescribing information. Bridgewater, NJ; 2006 Mar.
102. Warner Chilcott. Mandelamine (methenamine mandelate) prescribing information. Rockaway, NJ; 2006 Oct.
a. AHFS Drug Information 2007. McEvoy GK, ed. Methenamine. Bethesda, MD: American Society of Health-System Pharmacists; 2007:889-90.
More Methenamine Mandelate resources
- Methenamine Mandelate Side Effects (in more detail)
- Methenamine Mandelate Dosage
- Methenamine Mandelate Use in Pregnancy & Breastfeeding
- Drug Images
- Methenamine Mandelate Drug Interactions
- Methenamine Mandelate Support Group
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- Methenamine Prescribing Information (FDA)
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- Hiprex Advanced Consumer (Micromedex) - Includes Dosage Information
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