Monurol Information
Monurol (Fosfomycin tromethamine)
Monurol (Fosfomycin tromethamine) Description
Monurol (Fosfomycin tromethamine) sachet contains fosfomycin tromethamine, a synthetic, broad spectrum, bactericidal antibiotic for oral administration. It is available as a single-dose sachet which contains white granules consisting of 5.631 grams of fosfomycin tromethamine (equivalent to 3 grams of fosfomycin), and the following inactive ingredients: mandarin flavor, orange flavor, saccharin, and sucrose. The contents of the sachet must be dissolved in water. Fosfomycin tromethamine, a phosphonic acid derivative, is available as (1,2S)-(1,2-epoxypropyl)phosphonic acid, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1). It is a white granular compound with a molecular weight of 259.2. Its empirical formula is CHOP.CHNO, and its chemical structure is as follows:
Monurol (Fosfomycin tromethamine) Clinical Pharmacology
Absorption:
Cimetidine does not affect the pharmacokinetics of fosfomycin when coadministered with Monurol (Fosfomycin tromethamine) . Metoclopramide lowers the serum concentrations and urinary excretion of fosfomycin when coadministered with Monurol (Fosfomycin tromethamine) . (See)
Distribution:
ss
Fosfomycin is distributed to the kidneys, bladder wall, prostate, and seminal vesicles. Following a 50 mg/Kg dose of fosfomycin to patients undergoing urological surgery for bladder carcinoma, the mean concentration of fosfomycin in the bladder, taken at a distance from the neoplastic site, was 18.0 μg per gram of tissue at 3 hours after dosing. Fosfomycin has been shown to cross the placental barrier in animals and man.
Excretion:
A mean urine fosfomycin concentration of 706 (± 466) μg/mL was attained within 2-4 hours after a single oral 3-gm dose of Monurol (Fosfomycin tromethamine) under fasting conditions. The mean urinary concentration of fosfomycin was 10 μg/mL in samples collected 72-84 hours following a single oral dose of Monurol (Fosfomycin tromethamine) .
Following a 3-gm dose of Monurol (Fosfomycin tromethamine) administered with a high fat meal, a mean urine fosfomycin concentration of 537 (± 252) μg/mL was attained within 6-8 hours. Although the rate of urinary excretion of fosfomycin was reduced under fed conditions, the cumulative amount of fosfomycin excreted in the urine was the same, 1118 (± 201) mg (fed) vs. 1140 mg (± 238) (fasting). Further, urinary concentrations equal to or greaterthan 100 μg/mL were maintained for the same duration, 26 hours, indicating that Monurol (Fosfomycin tromethamine) can be taken without regard to food.
Following oral administration of Monurol (Fosfomycin tromethamine) , the mean half-life for elimination (t) is 5.7 (± 2.8) hours.
Fosfomycin (the active component of fosfomycin tromethamine) hasactivity against a broad range of gram-positive and gram-negative aerobic microorganisms which are associated with uncomplicated urinary tract infections. Fosfomycin is bactericidal in urine at therapeutic doses. The bactericidal action of fosfomycin is due to its inactivation of the enzyme enolpyruvyl transferase, thereby irreversibly blocking the condensation of uridine diphosphate-N-acetylglucosamine with p-enolpyruvate, one of the first steps in bacterial cell wall synthesis. It also reduces adherence of bacteria to uroepithelial cells.
There is generally no cross-resistance between fosfomycin and other classes of antibacterial agents such as beta-lactams and aminoglycosides.
Fosfomycin has been shown to be active against most strains of the following microorganisms, bothand in clinical infections as described in thesection:
Monurol (Fosfomycin tromethamine) Indications And Usage
Monurol (Fosfomycin tromethamine) is indicated only for the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains ofMonurol (Fosfomycin tromethamine) is not indicated for the treatment of pyelonephritis or perinephric abscess.
If persistence or reappearance of bacteriuria occurs after treatment with Monurol (Fosfomycin tromethamine) , other therapeutic agents should be selected. (Seeandsection)
Monurol (Fosfomycin tromethamine) Contraindications
Monurol (Fosfomycin tromethamine) is contraindicated in patients with known hypersensitivity to the drug.
Monurol (Fosfomycin tromethamine) Warnings
If CDAD is suspected or confirmed, ongoing antibiotic use not directed againstmay need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of, and surgical evaluation should be instituted as clinically indicated.
Monurol (Fosfomycin tromethamine) Adverse Reactions
In clinical studies, drug related adverse events which were reported in greater than 1% of the fosfomycin-treated study population are listed below:
In clinical trials, the most frequently reported adverse events occurring in > 1 % of the study population regardless of drug relationship were:diarrhea 10.4%, headache 10.3%, vaginitis 7.6%, nausea 5.2%, rhinitis 4.5%, back pain 3.0%, dysmenorrheal 2.6%, pharyngitis 2.5%, dizziness 2.3%, abdominal pain 2.2%, pain 2.2%, dyspepsia 1.8%, asthenia 1.7%, and rash 1.4%.
The following adverse events occurred in clinical trials at a rate of less than 1%, regardless of drug relationship:abnormal stools, anorexia, constipation, dry mouth, dysuria, ear disorder, fever, flatulence, flu syndrome, hematuria, infection, insomnia, lymphadenopathy, menstrual disorder, migraine, myalgia, nervousness, paresthesia, pruritus, SGPT increased, skin disorder, somnolence, and vomiting.
One patient developed unilateral optic neuritis, an event considered possibly related to Monurol (Fosfomycin tromethamine) therapy.
Serious adverse events from the marketing experience with Monurol (Fosfomycin tromethamine) outside of the United States have been rarely reported and include: angioedema, aplastic anemia, asthma (exacerbation), cholestatic jaundice, hepatic necrosis, and toxic megacolon.
Although causality has not been established, during post marketing surveillance, the following events have occurred in patients prescribed Monurol (Fosfomycin tromethamine) : anaphylaxis and hearing loss.
Monurol (Fosfomycin tromethamine) Overdosage
In acute toxicology studies, oral administration of high doses of Monurol (Fosfomycin tromethamine) up to 5 gm/kg were well-tolerated in mice and rats, produced transient and minor incidences of watery stools in rabbits, and produced diarrhea with anorexia in dogs occurring 2-3 days after single dose administration. These doses represent 50-125 times the human therapeutic dose.
The following events have been observed in patients who have taken Monurol (Fosfomycin tromethamine) in overdose: vestibular loss, impaired hearing, metallic taste, and general decline in taste perception. In the event of overdosage, treatment should be symptomatic and supportive.
Monurol (Fosfomycin tromethamine) Dosage And Administration
The recommended dosage for women 18 years of age and older for uncomplicated urinary tract infection (acute cystitis) is one sachet of Monurol (Fosfomycin tromethamine) . Monurol (Fosfomycin tromethamine) may be taken with or without food.
Monurol (Fosfomycin tromethamine) should not be taken in its dry form. Always mix Monurol (Fosfomycin tromethamine) with water before ingesting. (Seesection)
Monurol (Fosfomycin tromethamine) Preparation
Monurol (Fosfomycin tromethamine) should be taken orally. Pour the entire contents of a single-dose sachet of Monurol (Fosfomycin tromethamine) into 3 to 4 ounces of water (1/2 cup) and stir to dissolve. Do not use hot water. Monurol (Fosfomycin tromethamine) should be taken immediately after dissolving in water.
Monurol (Fosfomycin tromethamine) How Supplied
Monurol (Fosfomycin tromethamine) is available as a single-dose sachet containing the equivalent of 3 grams of fosfomycin.
NDC # 0456-4300-08
Keep this and all drugs out of the reach of children.
Manufactured by:Zambon Switzerland Ltd.Division of Zambon Group, SpAVia Industria 136814 Cadempino, Switzerland
Made in Switzerland
Distributed by:Forest Pharmaceuticals, Inc.Subsidiary of Forest Laboratories, Inc.St. Louis, MO 63045
Monurol (Fosfomycin tromethamine) Clinical Studies
In controlled, double-blind studies of acute cystitis performed in the United States, a single-dose of Monurol (Fosfomycin tromethamine) was compared to three other oral antibiotics (See table below). The study population consisted of patients with symptoms and signs of acute cystitis of less than 4 days duration, no manifestations of upper tract infection (e.g., flank pain, chills, fever), no history of recurrent urinary tract infections (20% of patients in the clinical studies had a prior episode of acute cystitis within the preceding year), no known structural abnormalities, no clinical or laboratory evidence of hepatic dysfunction, and no known or suspected CNS disorders, such as epilepsy, or other factors which would predispose to seizures. In these studies, the following clinical success (resolution of symptoms) and microbiologic eradication rates were obtained
Rev. April 2011
RMC 237-02
Monurol (Fosfomycin tromethamine) Principal Display Panel – G Packet
NDC 0456-4300-08
(fosfomycin tromethamine)
(equivalent to 3 grams of fosfomycin)
Dissolve contents in 3 to 4 ounces of water. Drink immediately. Do not use hot water.
