FOMICYT Powder for solution for infusion Ref.[6865] Active ingredients: Fosfomycin

The daily dose of fosfomycin is determined based on the indication, severity and site of the infection, susceptibility of the pathogen(s) to fosfomycin and the renal function. In children, it is also determined by age and body weight.

Adults and adolescents ≥12 years of age (>40 kg)

Fosfomycin is primarily excreted renally unchanged.

The general dosage guidelines for adults with estimated creatinine clearance >80 ml/min are as follows:

Individual doses must not exceed 8 g.

^a The high-dose regimen in 3 divided doses should be used in severe infections expected or known to be caused by less susceptible bacteria.

There are limited safety data in particular for doses in excess of 16 g/day. Special caution is advised when such doses are prescribed.

Dosage in renal insufficiency

The dose recommendations for patients with renal impairment are based on pharmacokinetic modelling and limited clinical data; safety and efficacy have not yet been evaluated in clinical trials.

It is unclear if dose reductions are necessary for patients with an estimated creatinine clearance between 40–80 ml/min. Great caution should be exercised in these cases, particularly if doses at the higher end of the recommended range are considered.

In patients with impaired renal function the dose of fosfomycin must be adjusted to the degree of renal impairment.

Dose titration should be based on creatinine clearance values.

In adults, creatinine clearance may be calculated according to the following formula by Cockroft and Gault:

Creatinine clearance (CL_CR) in men [ml/min]: (140-age [years]) x body weight [kg] / 72 x serum creatinine [mg/dl]

In order to calculate CL_CR in women, the result of this formula is multiplied by 0.85.

Dosage table for patients with impaired renal function:

^a The dose is expressed as a proportion of the dose that would have been considered appropriate if the patient’s renal function were normal

The first dose should be increased by 100% (loading dose), but must not exceed 8 g.

Patients undergoing renal replacement therapy

Patients undergoing chronic intermittent dialysis (every 48 hours) should receive 2 g of fosfomycin at the end of each dialysis session.

During continuous veno-venous hemofiltration (post-dilution CVVHF), fosfomycin is effectively eliminated. Patients undergoing post-dilution CVVHF will not require any dose adjustment (see section 5.2).

No clinical data exist for intravenous fosfomycin in patients undergoing pre-dilution CVVHF or other forms of renal replacement therapy.

Hepatic impairment

There are no data indicating that dose adjustment is necessary in patients with hepatic impairment.

Elderly patients

The recommended doses for adults should be used in elderly patients. Caution is advised when considering the use of doses at the higher end of the recommended range (see also recommendations on dosage for patients with impaired renal function).

Paediatric population

Dose recommendations are based on very limited data.

Neonates, infants and children <12 years of age (<40 kg)

The dosage of fosfomycin in children should be based on age and body weight (BW):

^a Sum of gestational and postnatal age.
^b The high-dose regimen may be considered for severe infections and or serious infections (such as meningitis), in particular when known or suspected to be caused by organisms with moderate susceptibility.

No dose recommendations can be made for children with renal impairment.

Method and duration of administration

Method of administration

Disodium fosfomycin is intended for intravenous administration. The duration of infusion should be at least 15 minutes for the 2 g pack size, at least 30 minutes for the 4 g pack size and at least 60 minutes for the 8 g pack size.

Use only clear solutions.

As damaging effects can result from inadvertent intra-arterial administration of products not specifically recommended for intra-arterial therapy, it is essential to ensure that fosfomycin is only administered into veins.

For preparation of the solution for infusion see section 6.6.

Duration of treatment

Treatment duration should take into account the type of infection, the severity of the infection as well as the patient’s clinical response. Relevant therapeutic guidelines should be adhered to when deciding treatment duration.

To date, no cases of accidental overdose with clinically relevant intolerances have been reported. If an overdose is believed to have taken place, the patient must be monitored (particularly for plasma/serum electrolyte levels) and treated symptomatically. Fosfomycin is effectively cleared from the body by haemodialysis with a mean elimination half-life of approximately 4 hours.

4 years.

Chemical and physical in-use stability of the reconstituted solution that has been produced under aseptic conditions has been demonstrated for 24 hours at 25°C if protected from light.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.

This medicinal product does not require any special storage conditions.

For storage of the reconstituted solution see section 6.3.

Clear type-II glass bottles with a rubber stopper (bromobutyl rubber) and pull-off cap containing 2 g (in 100 ml bottle), 4 g (in 100 ml bottle) or 8 g (in 250 ml bottle) of Fomicyt, respectively, in packs of 10 bottles each.

Not all pack sizes may be marketed.

For single use only.

Any unused product or waste material should be disposed of in accordance with local requirements.

Preparation of the solution for infusion

In order to prepare the solution for infusion:

Fomicyt 2 g should be dissolved in 50 ml of Water for Injections, Glucose Infusion 50 mg/ml (5%) or Glucose Infusion 100 mg/ml (10%).

Fomicyt 4 g should be dissolved in 100 ml of Water for Injections, Glucose Infusion 50 mg/ml (5%) or Glucose Infusion 100 mg/ml (10%).

Fomicyt 8 g should be dissolved in 200 ml of Water for Injections, Glucose Infusion 50 mg/ml (5%) or Glucose Infusion 100 mg/ml (10%).

A slight degree of warming occurs when the powder is dissolved.

The reconstituted solution is clear and colourless to slightly yellowish.

Displacement value

The displacement values for the reconstituted solutions are 1 ml for the 2 g pack size, 2 ml for the 4 g pack size and 4 ml for the 8 g pack size.

These volumes are equivalent to an increase of volume of 2%. This has to be considered when preparing the final solution in case of not using the entire content of the bottle.