This information is intended for use by health professionals
Monuril 3 g granules for oral solution
One sachet contains 5.631 g of fosfomycin trometamol equivalent to 3.0 g fosfomycin
Excipient(s) with known effect:
One sachet contains 2.213 g of sucrose, see section 4.4.
For the full list of excipients, see section 6.1.
Granules for oral solution.
Monuril is indicated for (see section 5.1):
- the treatment of acute, uncomplicated cystitis in women and female adolescents
- perioperative antibiotic prophylaxis for transrectal prostate biopsy in adult man
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Acute, uncomplicated cystitis in women and female adolescents (>12 years of age): 3 g fosfomycin once
Perioperative antibiotic prophylaxis for transrectal prostate biopsy: 3 g fosfomycin 3 hours prior to the procedure and 3 g fosfomycin 24 hours after the procedure.
Use of Monuril is not recommended in patients with renal impairment (creatinin clearance < 10 ml/min, see section 5.2).
The safety and efficacy of Monuril in children aged below 12 years of age have not been established.
Method of administration
For oral use.
For the indication of acute, uncomplicated cystitis in women and female adolescents it should be taken on an empty stomach (about 2-3 hours before or 2-3 hours after a meal), preferably before bedtime and after emptying the bladder.
The dose should be dissolved into a glass of water and taken immediately after its preparation.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Serious and occasionally fatal hypersensitivity reactions, including anaphylaxis and anaphylactic shock, may occur during fosfomycin treatment (see sections 4.3 and 4.8). If such reactions occur, treatment with fosfomycin must be discontinued immediately and adequate emergency measures must be initiated.
Clostridioides difficile -associated diarrhea
Clostridioides difficile-associated colitis and pseudo-membranous colitis have been reported with fosfomycin and may range in severity from mild to life-threatening (see section 4.8). Therefore, it is important to consider this diagnosis in patients who present with diarrhea during or subsequent to the administration of fosfomycin. Discontinuation of therapy with fosfomycin and the administration of specific treatment for Clostridioides difficile should be considered. Medicinal products that inhibit peristalsis should not be given.
The safety and efficacy of Monuril in children below 12 years of age have not been established. Therefore, this medicine should not be used in this age group (see section 4.2).
Persistent infections and male patients
In case of persistent infections, a thorough examination and a re-evaluation of the diagnosis is recommended as this is often due to complicated urinary tract infections or the prevalence of resistant pathogens (e.g. Staphylococcus saprophyticus, see section 5.1). In general, urinary tract infections in male patients have to be considered as complicated UTIs for which this medicinal product is not indicated (see section 4.1).
This medicine contains less than 1 mmol sodium (23 mg) per sachet that is to say essentially 'sodium-free'.
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not use this medicine.
May rarely cause severe hypersensitivity reactions and bronchospasm.
Concomitant administration of metoclopramide has been shown to lower serum and urinary concentrations of fosfomycin and should be avoided.
Other medicinal products that increase gastrointestinal motility may produce similar effects.
Food may delay the absorption of fosfomycin, with consequent slight decrease in peak plasma levels and urinary concentrations. It is therefore preferable to take the medicinal product on an empty stomach or about 2 – 3 hours after meals.
Specific problems concerning the alteration in INR:
Numerous cases of increased oral anticoagulant activity have been reported in patients receiving antibiotic therapy. Risk factors include severe infection or inflammation, age and poor general health. Under these circumstances, it is difficult to determinate whether the alteration in INR is due to the infectious disease or its treatment. However, certain classes of antibiotics are more often involved and in particular: fluoroquinolones, macrolides, cyclins, cotrimoxazole and certain cephalosporins.
Interaction studies have only been performed in adults.
Only limited data on the safety of fosfomycin treatment during 1st trimester of pregnancy (n=152) are available. These data do not raise any safety signal for teratogenicity so far. Fosfomycin crosses the placenta.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).
Monuril should only be used during pregnancy, if clearly necessary.
Fosfomycin is excreted in human milk in low quantities. If clearly necessary, a single dose of oral fosfomycin can be used during breast-feeding.
No data in humans are available. In male and female rats oral administration of fosfomycin up to 1000 mg/kg/d did not impair fertility.
No specific studies have been performed but patients should be informed that dizziness has been reported. This may influence some patients' ability to drive and use machines (see section 4.8).
Summary of the safety profile
The most common adverse reactions following the single-dose administration of fosfomycin trometamol involve the gastrointestinal tract, mainly diarrhoea. These events are usually self-limited in duration and resolve spontaneously.
Tabulated list of adverse reactions
The following table displays adverse reactions that have been reported with the use of fosfomycin trometamol from either clinical-trial or post-marketing experiences.
Undesirable effects are listed by body system and frequency using the following convention:
Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated form the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
System organ class
Adverse drug reactions
Infections and infestations
Immune system disorders
Anaphylactic reactions including anaphylactic shock, hypersensitivity (see section 4.4)
Nervous system disorders
Diarrhoea, nausea, dyspepsia, abdominal pain
Antibiotic- associated colitis (see section 4.4)
Skin and subcutaneous tissue disorders
Rash, urticaria, pruritus
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system website: www.mhra.gov.uk/yellowcard.
Experience regarding the overdose of oral fosfomycin is limited. Cases of hypotonia, somnolence, electrolytes disturbances, thrombocytopenia and hypoprothrombinemia have been reported with parenteral use of fosfomycin.
In the event of overdose, the patient must be monitored (particularly for plasma/serum electrolyte levels), and treatment should be symptomatic and supportive. Rehydration is recommended to promote urinary elimination of the active substance. Fosfomycin is effectively cleared from the body by haemodialysis with a mean elimination half-life of approximately 4 hours.
Pharmacotherapeutic group: Antibacterials for systemic use – other antibacterials.
ATC code: J01XX01
Mechanism of action:
Fosfomycin exerts a bactericidal effect on proliferating pathogens by preventing the enzymatic synthesis of the bacterial cell wall. Fosfomycin inhibits the first stage of intracellular bacterial cell wall synthesis by blocking peptidoglycan synthesis.
Fosfomycin is actively transported into the bacterial cell via two different transport systems (the sn-glycerol-3-phosphate and hexose-6 transport systems).
Limited data indicate that fosfomycin most likely acts in a time-dependent manner.
Mechanism of resistance
Main mechanism of resistance is a chromosomal mutation causing an alteration of the bacterial fosfomycin transport systems. Further resistance mechanisms, which are plasmid- or transposon-borne, cause enzymatic inactivation of fosfomycin by binding the molecule to glutathione or by cleavage of the carbon-phosphorus-bond in the fosfomycin molecule, respectively.
Cross-resistance between fosfomycin and other antibiotic classes is not known.
Susceptibility testing breakpoints
The susceptibility breakpoints established by the European Committee on Antimicrobial Susceptibility Testing are as follows (EUCAST breakpoint table version 11):
≤ 8 mg/L
> 8 mg/L
Prevalence of acquired resistance
The prevalence of acquired resistance of individual species may vary geographically and over time. Local information about the resistance situation is therefore necessary, particularly in order to ensure appropriate treatment of severe infections.
The following table is based on data from surveillance programs and studies. It comprises organisms relevant for the approved indications:
Commonly susceptible species
Aerobic Gram-negative microorganisms
Species in which acquired resistance may be a problem
Aerobic Gram-positive microorganisms
Aerobic Gram-negative microorganisms
Inherently resistant species
Aerobic Gram-positive microorganisms
After single-dose oral administration, fosfomycin trometamol has an absolute bioavailability of about 33-53%. Rate and extent of absorption are reduced by food, but the total amount of active substance excreted in the urine over time is the same. Mean urinary fosfomycin concentrations are maintained above an MIC threshold of 128 μg/mL for at least 24 h post 3 g oral dose in either the fasting or fed state, but the time to reach maximal concentrations in urine are delayed by 4 h. Fosfomycin trometamol undergoes enterohepatic recirculation.
Fosfomycin does not appear to be metabolised. Fosfomycin is distributed to tissues including the kidneys and bladder wall. Fosfomycin is not bound to plasma proteins and crosses the placental barrier.
Fosfomycin is excreted unchanged mainly via the kidneys by glomerular filtration (40-50% of the dose is found in the urine) with an elimination half-life of about 4 hours after oral use and to a lesser extent in faeces (18-28% of the dose). Even if food delays drug absorption, the total amount of drug excreted in the urine over time is the same.
In patients with impaired renal function, the elimination half-life is increased proportionally to the degree of renal insufficiency. Urinary concentrations of fosfomycin in patients with impaired renal function remain effective for 48 hours after a usual dose if creatinine clearance is above 10 ml/min.
In older people fosfomycin clearance is reduced in line with the age related reduction in renal function.
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity or toxicity to reproduction.
No carcinogenicity data are available for Fosfomycin.
After reconstitution in water, the solution is stable at room temperature for 24 hours.
Store away from direct sunlight.
Sachets are a four layer laminate: paper, polyethylene, aluminium, polyethylene.
Sachets are supplied in cardboard outer containing 1 sachet, 2 sachets or 5 sachets.
Not all pack sizes may be marketed.
The dose must be dissolved in a glass of water and administered soon after dissolving.
Any unused product or waste material should be disposed in accordance with local requirements.
Via Lillo Del Duca, 10
20091 Bresso (Milan) – Italy
Tel: +39 02 665 241
Fax: +39 02 665 01 492
18/03/1994 / 19/09/2008