Monurol

Generic Name: Fosfomycin Tromethamine
Class: Urinary Anti-infectives
VA Class: AM900
Chemical Name: (1R,2S)-(1,2-Epoxypropyl)phosphonic acid, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1)
Molecular Formula: C3H7O4P•C4H11N O13
CAS Number: 78964-85-9

Introduction

Antibacterial; phosphonic acid derivative.1

Uses for Monurol

Urinary Tract Infections (UTIs)

Treatment of uncomplicated UTIs (acute cystitis) in women when UTIs are caused by susceptible Escherichia coli or Enterococcus faecalis (formerly Streptococcus faecalis).1 2 3 4 5

Slideshow: The Shocking Truth About Antibiotic Resistance

Do not use for treatment of pyelonephritis or perinephric abscesses.1

If persistence or reappearance of bacteriuria occurs after fosfomycin treatment, do not repeat treatment; select another anti-infective.1

Monurol Dosage and Administration

Administration

Oral Administration

Administer orally.1

May be taken with or without food.1

Prepare oral solution by adding contents of a single-dose packet (sachet) containing 3 g of the drug to 90–120 mL of water;1 do not use hot water.1 Ingest immediately after preparation.1

Do not administer as dry granules.1

Dosage

Available as fosfomycin tromethamine; dosage expressed in terms of fosfomycin.1

Adults

Urinary Tract Infections (UTIs)
Uncomplicated UTIs
Oral

3 g as a single dose.1

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.1

Renal Impairment

Dosage adjustment not necessary.6 (See Pharmacokinetics.)

Geriatric Patients

Dosage adjustment not necessary.1 (See Geriatric Use under Cautions.)

Cautions for Monurol

Contraindications

  • Known hypersensitivity to fosfomycin or any ingredient in the formulation.1

Warnings/Precautions

General Precautions

Retreatment

Do not use more than a single dose to treat a single episode of acute cystitis; repeated daily doses do not enhance efficacy and increase incidence of adverse events.1

Selection and Use of Anti-infectives

Obtain urine specimens for culture and in vitro susceptibility testing before and after completion of therapy.1

To reduce development of drug-resistant bacteria and maintain effectiveness of fosfomycin and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.1

Specific Populations

Pregnancy

Category B.1

Lactation

Not known whether distributed into breast milk.1

Potential for serious adverse reactions in nursing infants; discontinue nursing or do not administer drug.1

Pediatric Use

Safety and efficacy not established in children ≤12 years of age.1 Manufacturer make no specific dosage recommendations for pediatric patients.1

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.1 No evidence of substantial differences in safety and efficacy relative to younger adults.1

Although dosage adjustment not usually necessary, select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.1

Common Adverse Effects

Diarrhea.1

Interactions for Monurol

Drugs that Increase GI Motility

May decrease serum and urine concentrations of fosfomycin.1

Specific Drugs

Drug

Interaction

Comments

Cimetidine

Pharmacokinetics of fosfomycin not affected1

Metoclopramide

Decreased serum concentrations and decreased urinary excretion of fosfomycin1

Monurol Pharmacokinetics

Absorption

Bioavailability

Fosfomycin tromethamine is rapidly absorbed following oral administration and converted to the free acid, fosfomycin.1 Peak serum concentrations attained within 2–4 hours.1

Food

Food decreases oral bioavailability;1 bioavailability is 37% and 30% under fasting and fed conditions, respectively.1

Cumulative amount of drug excreted in urine is similar whether the drug is given with or without food.1

Distribution

Extent

Distributed to kidneys, bladder wall, prostate, and seminal vesicles.1

Crosses the placenta.1

Plasma Protein Binding

Not bound to plasma proteins.1

Elimination

Elimination Route

Eliminated unchanged in urine (38% of an oral dose) and feces (18% of an oral dose).1

Peak urine concentrations achieved within 2–4 hours or 6–8 hours under fasting or fed conditions, respectively; cumulative amount excreted in urine is similar.1

Half-life

5.7 hours.1

Special Populations

Geriatric adults: Pharmacokinetics similar to that reported in younger adults.1

Renal impairment: Decreased elimination and prolonged half-life.1 Half-life ranges up to 50 hours in patients with renal impairment.1

Stability

Storage

Oral

Powder

25°C (may be exposed to 15–30°C).1

Actions and Spectrum

  • Phosphonic acid derivative,5 synthetic antibacterial agent.1

  • Bactericidal in urine when administered in therapeutic doses.1 5

  • Antibacterial activity results from interference with bacterial cell wall synthesis by inhibiting the enzyme enolpyruvyl transferase that catalyzes the formation of uridine diphosphate-N-acetylmuramic acid in the first step of bacterial cell wall synthesis.1 4 5 Also reduces adherence of bacteria to uroepithelial cells.1 5

  • Active in vitro against a broad spectrum of gram-negative and gram-positive bacteria, including those commonly associated with uncomplicated UTIs.1 4 5 Active in vitro and in vivo against Escherichia coli and Enterococcus faecalis.1

  • Cross-resistance generally does not occur between fosfomycin and other antibacterial agents (e.g., β-lactams, aminoglycosides).1

Advice to Patients

  • Importance of diluting granules with water (not hot water) just prior to administration.1

  • Advise patient that fosfomycin may be taken with or without food.1

  • Importance of contacting clinician if UTI symptoms do not improve within 2–3 days after treatment.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

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

Fosfomycin Tromethamine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For solution

3 g (of fosfomycin) per packet

Monurol Sachet

Forest

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Monurol 3GM Packet (FOREST): 1/$50.86 or 3/$139.89

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions January 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Forest Pharmaceuticals, Inc. Monurol (fosfomycin tromethamine) powder prescribing information. St. Louis, MO; 2004 May.

2. Elhanan G, Tabenkin H, Yahalom R et al. Single-dose fosfomycin trometamol versus 5-day cephalexin regimen for treatment of uncomplicated lower urinary tract infections in women. Antimicrob Agents Chemother. 1994; 38:2612-4. [IDIS 337800] [PubMed 7872756]

3. Selvaggi FP, Ditonno P, Traficante A et al. Fosfomycin trometamol (Monuril) versus norfloxacin in single dose for adult female uncomplicated UTIs: multicenter randomized, double-blind study. Chemotherapy. 1990; 36(Suppl 1):31-3. [IDIS 297402] [PubMed 2085986]

4. Reeves DS. Fosfomycin trometamol. J Antimicrob Chemother. 1994; 34:853-8. [IDIS 343321] [PubMed 7730229]

5. Patel SS, Balfour JA, Bryson HM. Fosfomycin tromethamine: a review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections. Drugs. 1997; 53:637-56. [PubMed 9098664]

6. Forest Pharmaceuticals, Inc, St. Louis, MO: Personal communication.

Hide
(web1)