Consumer medicine information

Monurol

Fosfomycin

BRAND INFORMATION

Brand name

Monurol

Active ingredient

Fosfomycin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Monurol.

SUMMARY CMI

MONUROL®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about taking this medicine, speak to your doctor or pharmacist.

1. Why am I taking MONUROL?

MONUROL contains the active ingredient fosfomycin trometamol. MONUROL is a single dose antibiotic used to treat uncomplicated urinary tract infections in females.

For more information, see Section 1. Why am I taking MONUROL? in the full CMI.

2. What should I know before I take MONUROL?

Do not take if you have ever had an allergic reaction to fosfomycin trometamol or any of the ingredients listed at the end of the CMI. Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I take MONUROL? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with MONUROL and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take MONUROL?

One sachet of MONUROL, dissolved in a glass of cold water and taken on an empty stomach, before bed and after emptying the bladder.

More instructions can be found in Section 4. How do I take MONUROL? in the full CMI.

5. What should I know while taking MONUROL?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are taking MONUROL.
  • If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine.
  • If you become pregnant while taking this medicine, tell your doctor immediately.
  • If you are about to have any blood tests, tell your doctor that you are taking this medicine.
Things you should not do
  • Do not take MONUROL to treat any other complaints unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if they have the same condition as you.
Driving or using machines
  • If you experience dizziness, do not drive, operate machinery or do anything else that could be dangerous.
Drinking alcohol
  • Tell your doctor if you drink alcohol.
Looking after your medicine
  • Keep your sachet in the carton until it is time to take them.
  • Store it in a cool dry place away from moisture, heat or sunlight.

For more information, see Section 5. What should I know while taking MONUROL? in the full CMI.

6. Are there any side effects?

Common side effects: headache, dizziness, diarrhoea (if it becomes severe consult your doctor immediately), nausea, vomiting, indigestion, infection of the female genital organs with symptoms like inflammation, irritation, itching, abdominal pain, rash, urticaria, pruritus. Serious side effects: mild to severe abdominal cramps, bloody stools, diarrhoea and/or fever. Serious signs that you may be having an allergic reaction include swelling of the face, lips, tongue or throat with breathing difficulties.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

MONUROL®

Active ingredient: fosfomycin trometamol

Consumer Medicine Information (CMI)

This leaflet provides important information about taking MONUROL. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about taking MONUROL.

Where to find information in this leaflet:

1. Why am I taking MONUROL?
2. What should I know before I take MONUROL?
3. What if I am taking other medicines?
4. How do I take MONUROL?
5. What should I know while taking MONUROL?
6. Are there any side effects?
7. Product details

1. Why am I taking MONUROL?

MONUROL contains the active ingredient fosfomycin trometamol. Fosfomycin trometamol is an antibiotic that has activity against E.coli and E. facaelis bacteria.

MONUROL is used to treat uncomplicated urinary tract infections in females. It works by killing bacteria which can cause infections.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

2. What should I know before I take MONUROL?

Warnings

Do not take MONUROL if:

  • you are allergic to fosfomycin trometamol, or any of the ingredients listed at the end of this leaflet.
    Always check the ingredients to make sure you can take this medicine.

Do not give this medicine to a child under the age of 12 years. Safety and effectiveness in children younger than 12 years have not been established.

Use is not recommended if you have severely reduced kidney function (creatinine clearance below 10 ml/min).

Check with your doctor if you:

  • have allergies to any other medicines, foods, preservatives or dyes.
  • take any medicines for any other condition.
  • Have or have had any other medical conditions such as:
    - an intolerance to some sugars
    - diarrhoea after taking any antibiotics
    - reduced kidney function, but your creatinine clearance is above 10 ml/min.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

Your doctor can discuss with you the risks and benefits involved.

If you are pregnant, the active ingredient in MONUROL can cross the placenta and MONUROL can pass into the foetus. There is a possibility that your baby may be affected.

The active ingredient in MONUROL passes into breast milk and there is a possibility that your baby may be affected.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and MONUROL may interfere with each other. These include:

  • metoclopramide or other drugs that increase the movement of food through the stomach and intestines, because they may reduce the uptake of fosfomycin trometamol by your body.
  • anticoagulants, as their ability to prevent your blood from clotting might be altered by fosfomycin trometamol and other antibiotics.
  • urinary alkalinisers (e.g. Ural®) or acidic drinks (e.g. cranberry juice) can alter the acidity of the urine and may interfere with how MONUROL works. Therefore use of MONUROL with these agents is not recommended.

These medicines or products may be affected by MONUROL or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect MONUROL.

4. How do I take MONUROL?

How much to take

  • The recommended dose is one sachet of MONUROL, given once, as a single dose dissolved in a glass of cold water.
  • Follow the instructions provided when MONUROL was prescribed.

When to take MONUROL

  • Take your medicine on an empty stomach, (2-3 hours before or 2-3 hours after a meal), preferably before going to bed and after emptying the bladder. MONUROL works most efficiently under these conditions.

How to take MONUROL

  • Dissolve the content of one sachet in a glass of water and drink immediately (do not use hot water).

If you forget to take MONUROL

If you forget to take it after filling your prescription, take it the very next day.

If you take too much MONUROL

If you think that you have taken too much MONUROL, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while taking MONUROL?

Things you should do:

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking MONUROL.

Remind any doctor, dentist or pharmacist you visit that you are taking MONUROL.

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

If you become pregnant while taking this medicine, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are taking this medicine. It may interfere with the results of some tests.

Keep all of your doctor's appointments so that your progress can be checked.

Things you should not do:

  • Do not take MONUROL to treat any other complaints unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if they have the same condition as you.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how MONUROL affects you.

MONUROL may cause dizziness in some people

If you have experienced this symptom, do not drive, operate machinery or do anything else that could be dangerous.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

  • Keep your sachet in the carton until it is time to take it. If you take the sachet out of the carton it may not keep well.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on windowsills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to take this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not take this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects with MONUROL, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • headache
  • dizziness
  • diarrhoea (if it becomes severe consult your doctor immediately)
  • nausea, vomiting
  • indigestion (dyspepsia)
  • infection of the female genital organs with symptoms like inflammation, irritation, itching (vulvovaginitis)
  • abdominal pain
  • rash, urticaria, pruritus
Speak to your doctor if you have any of these less serious side effects and they worry you

Serious side effects

Serious side effectsWhat to do
  • mild to severe abdominal cramps, bloody stools, diarrhoea and/or fever may mean that you have an infection of the large intestine (antibiotic-associated colitis)

Serious signs of an allergic reaction to MONUROL:

  • sudden onset of rash, itching or hives on the skin and or shortness of breath, wheezing or difficulty in breathing
  • swelling of the face, lips, tongue or throat with breathing difficulties (angioedema)
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What MONUROL contains

Active ingredient
(main ingredient)		5.631 g of fosfomycin trometamol as the active ingredient, equivalent to 3 g of fosfomycin
Other ingredients
(inactive ingredients)
  • tangerine flavour
  • orange flavour
  • saccharin
  • sucrose (MONUROL contains 2.213 g of sucrose).
Potential allergensThis medicine does not contain lactose, gluten, tartrazine or any other azo dyes.

Do not take this medicine if you are allergic to any of these ingredients.

What MONUROL looks like

MONUROL is presented as white granules for oral solution in a single use sachet.

The sachet is a four-layer laminate, comprising of: paper/polyethylene/aluminium/ polyethylene.

MONUROL sachet is supplied in an outer cardboard carton, one sachet per carton. (Aust R 278658).

Who distributes MONUROL?

Australia
Mayne Pharma International Pty Ltd
1538 Main North Road
Salisbury South, SA 5106

This leaflet was prepared in May 2025.

Published by MIMS July 2025

BRAND INFORMATION

Brand name

Monurol

Active ingredient

Fosfomycin

Schedule

S4

 

1 Name of Medicine

Fosfomycin trometamol.

2 Qualitative and Quantitative Composition

One sachet of Monurol granules for oral solution contains 5.631 g of fosfomycin trometamol equivalent to 3.0 g fosfomycin.
Fosfomycin trometamol is a white or nearly white crystalline powder. It is very soluble in water, slightly soluble in 95% methanol and ethanol, almost insoluble in anhydrous acetone, in ether and in chlorinated solvents.

Excipients with known effect.

Monurol contains sugars (as sucrose) and saccharin.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Monurol contains 3 g fosfomycin (as fosfomycin trometamol), presented as white granules for oral solution in single use sachet.

4 Clinical Particulars

4.1 Therapeutic Indications

Monurol is indicated only for the treatment of acute uncomplicated lower urinary tract infections (acute cystitis) in females above 12 years of age caused by the following susceptible pathogens: Escherichia coli or, Enterococcus faecalis.
Monurol is not indicated for the treatment of pyelonephritis or perinephric abscess or where resistance is likely (previous treatment failure, infection due to non-susceptible organism).
Appropriate culture and susceptibility studies should be performed to identify the causative organism(s) and determine its (their) susceptibility to Monurol. However, therapy may be initiated before results of these tests are known; once results become available, appropriate therapy should be continued. Consideration should be given to the relevant clinical guidelines on the appropriate use of antibacterial agents.

4.2 Dose and Method of Administration

The recommended dose for the treatment of an acute uncomplicated lower urinary tract infections (UTI) is a single Monurol sachet in women above 12 years of age.
Monurol is for oral administration.
It should be taken on an empty stomach or about 2 - 3 hours after meals, preferably before bedtime and after emptying the bladder.
The dose should be dissolved into a glass of cold water (do not use hot water) and taken immediately after its preparation.

Paediatric population.

The safety and efficacy of Monurol in children below 12 years has not been established. No data are available.

Renal impairment.

Use of Monurol is not recommended in patients with severe renal impairment (creatinine clearance < 10 mL/min, see Section 5.2 Pharmacokinetic Properties).

4.3 Contraindications

Hypersensitivity to fosfomycin trometamol or to any of the excipients (see Section 6.1 List of Excipients).

4.4 Special Warnings and Precautions for Use

General.

Do not use more than one single dose of Monurol to treat a single episode of acute uncomplicated lower UTI. Repeated daily doses of Monurol in an acute UTI did not improve the clinical success or microbiological eradication rates compared to single dose therapy, but did increase the incidence of adverse events.

Gender.

The three pivotal trials MON-US-01, MON-US-02 and MON-US-03 were conducted in female patients only. However, there is extensive early clinical trial and post-marketing experience in males. There do not appear to be any gender-associated differences in the safety profile of Monurol. Efficacy data in male patients with UTI is limited so Monurol is not recommended in males.

Hypersensitivity.

Hypersensitivity reactions, including anaphylaxis and anaphylactic shock, may occur during fosfomycin treatment and may be life-threatening (see Section 4.8 Adverse Effects (Undesirable Effects)). If such reaction occurs, fosfomycin should never be re-administrated and an adequate medical treatment is required.

Antibiotic-associated diarrhoea.

Antibiotic-associated diarrhoea has been reported with use of nearly all antibacterial agents, including fosfomycin. Diarrhoea may range in severity from mild to fatal colitis but is usually self-limited in duration and resolves spontaneously (see Section 4.8 Adverse Effects (Undesirable Effects)). Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with Monurol (including several weeks after treatment), may be symptomatic of Clostridium difficile-associated disease (CDAD). It is therefore important to consider this diagnosis in patients who develop serious diarrhoea during or after treatment with Monurol. If CDAD is suspected or confirmed, appropriate treatment should be initiated without delay.

Sucrose content.

Monurol contains sucrose. Its use is not recommended in patients with hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency.

Food.

Food may delay the absorption of the active ingredient of Monurol, with consequent slight decrease in peak plasma levels and urinary concentrations. It is therefore preferable to take the medicine on an empty stomach or about 2 - 3 hours after meals.

Use in hepatic impairment.

See Section 5.2 Pharmacokinetic Properties, Special populations.

Use in renal impairment.

In consideration of the safety profile of the drug and of single dose treatment, in patients with mild to moderate renal impairment (defined as creatinine clearance > 10 mL/min) it is not necessary to adjust the dose but these patients have to be carefully monitored.
Due to reduced excretion of drug and limited data, fosfomycin trometamol is contraindicated in severe renal failure (creatinine clearance < 10 mL/min), haemodialysis, peritoneal dialysis and haemofiltration.
Also see Section 4.2 Dose and Method of Administration; Section 5.2 Pharmacokinetic Properties, Special populations.

Use in the elderly.

Fosfomycin may be given in the elderly. In elderly patients with good renal function, pharmacokinetics, efficacy and safety appear similar to younger adults. For elderly patients with age-related or other renal insufficiency, see Section 5.2 Pharmacokinetic Properties, Special populations.

Paediatric use.

Experience in children with Monurol is limited. The product is not recommended for children below the age of 12.

Effects on laboratory tests.

In post-marketing surveillance, three cases of increased INR (prothrombin time) and two cases of decreased INR (prothrombin time) were reported. No further clinical information is available regarding these patients. As fosfomycin does not bind to plasma proteins and does not undergo metabolism, an interaction with anticoagulant drugs of the coumarin type such as warfarin is not anticipated, although fosfomycin has not been studied in patients taking anticoagulants. Recommend monitoring of coagulation in patients receiving coumarins.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concomitant administration of metoclopramide has been shown to lower serum and urinary concentrations of fosfomycin and should be avoided.
Other drugs that increase gastrointestinal motility may produce similar effects.
Cimetidine does not alter the pharmacokinetics of fosfomycin.
Interaction studies with metoclopramide and cimetidine have only been performed in healthy adult volunteers aged 20 years and over. No other drugs have been studied for potential interactions with fosfomycin. No drug interaction studies have been performed in humans aged less than 20 years.
Concomitant usage with urinary alkalinisers is not recommended. Monurol is most bactericidal at typical urinary pH. Also, potential for resistance development appears less at acidic pH.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fosfomycin had no effect on fertility in male and female rats at doses up to 1000 mg/kg/day (3-times the clinical dose relative to body surface area). No data are available in humans.
(Category B2)
Fosfomycin was not found to be teratogenic in rats and rabbits when tested at doses of up to 1000 mg/kg/day and 500 mg/kg/day, respectively (3- and 3.8-times the clinical dose relative to body surface area, respectively). Fetotoxicity was observed in rabbits at doses ≥ 1000 mg/kg/day, which was secondary to maternotoxicity (maternal deaths and body weight losses). No adverse findings were reported in peri-postnatal studies in rats treated at up to 1000 mg/kg/day (3-times the clinical dose relative to body surface area).
In early clinical trials and in the post-marketing period, at least 1552 pregnant human patients are known to have received fosfomycin during pregnancy, usually a 3 g single oral dose. Only limited data on the safety of fosfomycin treatment during the first trimester of pregnancy (n=152) are available. There is no evidence based on review of human data that fosfomycin is associated with adverse foetal or maternal outcomes or teratogenicity. At the present time, single-dose antibacterial treatments are not considered suitable to treat UTIs in pregnant women (also see Section 5.2 Pharmacokinetic Properties, Special populations).
 Fosfomycin is excreted in breast milk.
Monurol therapy should therefore not be used in breastfeeding mothers unless the potential benefit outweighs the potential risks.

4.7 Effects on Ability to Drive and Use Machines

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.

4.8 Adverse Effects (Undesirable Effects)

The majority of clinical trials have been conducted in adult or adolescent females aged 12 years or above. The most common adverse reactions following the single 3 g dose of fosfomycin trometamol involved the gastrointestinal tract, mainly diarrhoea. These events were usually self-limited in duration and resolve spontaneously. Table 1 lists drug-related adverse events which occurred in 1% or more of fosfomycin recipients in the three pivotal trials.
The following list displays adverse drug reactions that have been reported with the use of Monurol from either clinical-trial or post-marketing experiences.
The displayed frequency categories use 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).

Infections and infestations.

Common: vulvovaginitis.

Immune system disorders.

Not known: anaphylactic reactions including anaphylactic shock, hypersensitivity.

Nervous systems disorders.

Common: headache, dizziness.

Gastrointestinal disorders.

Common: diarrhoea, nausea, dyspepsia, abdominal pain.
Uncommon: vomiting, anorexia, dry mouth, flatulence.
Not known: antibiotic-associated colitis (see Section 4.4 Special Warnings and Precautions for Use, Antibiotic-associated diarrhoea).

Skin and subcutaneous tissue disorders.

Uncommon: rash, urticaria, pruritus.
Not known: angioedema.
One patient in a pivotal trial developed unilateral optic neuritis, considered possibly related to Monurol therapy.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

4.9 Overdose

In acute toxicity studies a single oral dose of 5000 mg/kg was well tolerated both in mice and rats and a single dose of 2000 mg/kg did not produce changes in rabbits and dogs.
Repeated dose studies by oral route showed that the no-effect dose was between 100 and 200 mg/kg after 4 weeks of treatment in dogs and rats, respectively.
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.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Fosfomycin inhibits the first stage of bacterial wall synthesis. It inhibits the phosphoenolpyruvate transferase enzyme, thereby irreversibly blocking the condensation of uridine diphosphate-N-acetylglucosamine with p-enolpyruvate.
Fosfomycin is actively transported into the bacterial cell via two different transport systems (the sn-glycerol-3-phosphate and hexose-6 transport systems). Fosfomycin has a mainly bactericidal action. It can also reduce bacterial adhesion to bladder mucosa, which can be a predisposing factor for recurring infections. As this mechanism of action is unique to fosfomycin cross-resistance is not expected with other antibiotics.

Microbiology.

The activity of fosfomycin against E. coli isolates causing uncomplicated UTIs in females greater than 12 years of age in Australia were tested by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) disk diffusion method. Isolates determined to be resistant by disk diffusion were retested by agar dilution susceptibility testing using EUCAST methodology. Based upon Table 2's breakpoints the local susceptibility data from these studies conducted in 2019 and 2020 determined that 99.3% (n=1033 isolates tested) and 99.6% (n=1023 isolates tested) were fosfomycin susceptible.

Activity in vitro.

Bacterial species commonly susceptible to fosfomycin using European Committee on Antimicrobial Susceptibility Testing (EUCAST) or Clinical and Laboratory Standard Institute (CLSI) susceptibility testing guidelines: Escherichia coli, Enterococcus faecalis.
Oral fosfomycin is not recommended in the treatment of the following bacterial species which do not have EUCAST or CLSI susceptibility testing guidelines: Staphylococcus saprophyticus, Pseudomonas aeruginosa, Enterococcus faecium, Staphylococcus aureus, Acinetobacter spp., Stenotrophomonas maltophilia, Bacteroides spp., Enterobacterales (other than E. coli), and other anaerobic bacteria.

Resistance.

Main mechanism of resistance is a chromosomal mutation causing an alteration of the bacterial fosfomycin transport systems. Plasmid-encoded mechanisms of resistance to fosfomycin have also been documented.
Based on EUCAST criteria, fosfomycin trometamol single 3 g oral dose is calibrated for the treatment of acute uncomplicated UTI caused by Escherichia coli. The minimum inhibitory concentration (MIC) breakpoints are ≤ 8 (less than or equal to) mg/L (S) and > 8 mg/L (R). EUCAST disk diffusion zone diameter breakpoints for E. coli only are ≥ 24 mm (S) and < 24 mm (R). All methods require glucose-6-phosphate supplementation.
There are no published EUCAST breakpoints for fosfomycin trometamol single 3 g oral dose for other urinary pathogens, such as Enterobacterales other than E. coli, Pseudomonas spp, Staphylococcus saprophyticus, or Enterococcus spp.
Based on CLSI criteria, only E. coli and Enterococcus faecalis from urinary tract isolates are calibrated. MIC breakpoints for both are ≤ 64 mg/L (S), 128 mg/L (I), and ≥ 256 mg/L (R). Disk and agar dilution MIC methods are approved provided there is supplemental glucose-6-phosphate. CLSI does not recommend broth dilution fosfomycin susceptibility testing.
There are no CLSI guidelines for any other bacteria apart from E. coli and Enterococcus faecalis.

Clinical efficacy against specific pathogens.

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable.
Oral fosfomycin should be used where there is resistance to other suitable antibiotics, including trimethoprim, cephalexin and amoxycillin/clavulanic acid.

Pharmacokinetic (PK)/pharmacodynamic (PD) relationship.

Limited data indicate that fosfomycin most likely acts in a concentration-dependent manner. There are no known PK/PD breakpoints for fosfomycin.

Clinical trials.

In three phase 3 prospective parallel multi-centre double-blind double-dummy randomised trials of acute uncomplicated UTI performed in the 1990s, a single 3 g oral dose of Monurol was compared to three other oral antibiotics (see Table 3). The study population consisted of female patients with symptoms and signs of acute lower UTI of less than 4 days duration, no manifestations of upper tract infection (e.g. flank pain, chills, fever), no history of recurrent UTIs (20% of patients in the clinical studies had a prior episode of acute uncomplicated lower UTI 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 the first two studies (MON-US-01 comparator arm ciprofloxacin and MON-US-02 comparator arm trimethoprim/sulphamethoxazole), adult females aged 18 years and older were enrolled and patients with renal dysfunction (defined as serum creatinine clearance < 30 mL/min) were excluded. In the third study (MON-US-03, nitrofurantoin comparator), females aged 12 years and older were enrolled and patients with severe renal dysfunction (defined as serum creatinine clearance < 60 mL/min) were excluded. In all three studies, pregnancy, immunosuppression and neutropenia were exclusion criteria.
In these studies, the following clinical success (resolution of symptoms) and microbiologic eradication rates were obtained (Table 3).
In the 3 pivotal studies, median age of patients enrolled was 27-32 years (fosfomycin) and 27-32 years (comparator arms). In all 3 studies, approximately half the patients were aged 30 years or less. The most common pathogen in the three pivotal studies was E. coli, which caused 82-86% of UTIs. Table 4 shows microbiological cure rates from pooled data from the 3 studies by pathogen.
There have been no other phase 3 prospective, parallel, multicentre, double-blind, double-dummy randomised efficacy and safety trials for the treatment of acute uncomplicated UTI since the three pivotal studies MON-US-01, MON-US-02, and MON-US-03 performed in the 1990s.

5.2 Pharmacokinetic Properties

Absorption.

After oral administration, fosfomycin is well absorbed from the gut and has an absolute bioavailability of about 35-40%. Food delays absorption, not influencing urinary concentrations.

Distribution.

Fosfomycin is distributed to the kidneys, bladder wall, prostate and seminal vesicles. Sustained concentrations of fosfomycin higher than the MIC are obtained in urine for 24-48 hours after oral administration.
Fosfomycin does not bind to plasma proteins, fosfomycin has been shown to cross the placental barrier in humans and animals.

Metabolism.

Fosfomycin does not appear to be metabolised.

Excretion.

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 and to a lesser extent in faeces (18-28% of the dose). The appearance of a second serum peak 6 and 10 hours after drug intake suggests that the drug is subject to enterohepatic recirculation.

Special populations.

Elderly.

The pharmacokinetic features of fosfomycin are not modified by age (see Section 4.4 Special Warnings and Precautions for Use, Use in the elderly).

Pregnancy.

The pharmacokinetic features of fosfomycin do not appear to be modified by pregnancy in a study of 4 pregnant patients (also see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).

Hepatic impairment.

The pharmacokinetic features of fosfomycin have not been studied in patients with impaired hepatic function. However, fosfomycin does not undergo hepatic metabolism and clearance is known to be predominantly renal with urinary excretion. Limited studies confirm that there is an enterohepatic recirculation which does not influence bioavailability (also see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Use in hepatic impairment).

Renal impairment.

The pharmacokinetics of fosfomycin trometamol have not been studied in patients undergoing peritoneal dialysis or haemofiltration.
In 5 anuric patients undergoing haemodialysis, the t1/2 of fosfomycin during haemodialysis was 40 hours. In patients with varying degrees of renal impairment (creatinine clearances varying from 54 mL/min to 7 mL/min), the t1/2 of fosfomycin increased from 11 hours to 50 hours. The percent of fosfomycin recovered in urine decreased from 32% to 11% indicating that renal impairment significantly decreases the excretion of fosfomycin.
The drug accumulates in patients with severe renal impairment but the significance of this is unknown. Linear relationships have been established between fosfomycin pharmacokinetic parameters and glomerular filtration rate.
Also see Section 4.3 Contraindications; Section 4.4 Special Warnings and Precautions for Use, Use in renal impairment.

5.3 Preclinical Safety Data

Genotoxicity.

Fosfomycin was not found to be genotoxic under in vitro (bacterial reverse mutation assay, mammalian mutation assay, chromosomal aberration test) or in vivo conditions (mouse micronucleus test).

Carcinogenicity.

Carcinogenicity studies in rodents have not been conducted. Based on the short-term use of fosfomycin and the lack of evidence of genotoxicity, fosfomycin is not anticipated to be carcinogenic.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each sachet of Monurol also contains the following excipients: Tangerine flavour PHP-139220, Orange Juice flavour PHS-192439, saccharin and 2.213 g of sucrose.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

The sachet is a four layer laminate comprising of paper, polyethylene, aluminium and polyethylene, and is supplied in an outer cardboard carton, one sachet per carton.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Chemically, fosfomycin trometamol is 2-hydroxy-1,1-bis (hydroxymethyl) ethylammonium (2R,3S)-(3-methyloxiran-2-yl) phosphonate and has the following chemical structure:
Molecular formula: C7H18NO7P.
Relative molecular mass: 259.2.

CAS number.

78964-85-9.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes