Fomicyt 40mg/ml Powder for Solution for
Summary of Product Characteristics Updated 11-Dec-2017 | Nordic Pharma Limited
1. Name of the medicinal product
Fomicyt 40 mg/ml powder for solution for infusion
2. Qualitative and quantitative composition
One ml of reconstituted solution contains 40 mg fosfomycin.
Each bottle with 2.69 g of powder contains 2.64 g disodium fosfomycin, corresponding to 2 g fosfomycin
and 0.64 g sodium, for reconstitution in 50 ml of solvent.
Each bottle with 5.38 g of powder contains 5.28 g disodium fosfomycin, corresponding to 4 g fosfomycin
and 1.28 g sodium, for reconstitution in 100 ml of solvent.
Each bottle with 10.76 g of powder contains 10.56 g disodium fosfomycin, corresponding to 8 g
fosfomycin and 2.56 g sodium, for reconstitution in 200 ml of solvent.
For a full list of excipients, see section 6.1.
3. Pharmaceutical form
Powder for solution for infusion.
White to cream-coloured powder.
4. Clinical particulars
4.1 Therapeutic indications
Fosfomycin is indicated for the treatment of the following infections in adults and children including
neonates (see section 5.1):
- Complicated urinary tract infections
- Nosocomial lower respiratory tract infections
- Bacterial meningitis
- Bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections
Fosfomycin should be used only when it is considered inappropriate to use antibacterial agents that are
commonly recommended for the initial treatment of the infections listed above, or when these alternative
antibacterial agents have failed to demonstrate efficacy.
For information regarding the combination with other antibiotics see section 4.4 and 4.5.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
4.2 Posology and method of administration
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:
in 2–3 divided doses
Complicated urinary tract infection
12–16 g in 2–3 divided doses
Nosocomial lower respiratory tract infection
in 2–3 divided doses
in 3–4 divided doses
Individual doses must not exceed 8 g.
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
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:
In order to calculate CL
in women, the result of this formula is multiplied by 0.85.
Dosage table for patients with impaired renal function:
Daily dosage recommended
70% (in 2–3 divided doses)
60% (in 2–3 divided doses)
40% (in 2–3 divided doses)
20% (in 1–2 divided doses)
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
No clinical data exist for intravenous fosfomycin in patients undergoing pre-dilution CVVHF or other
forms of renal replacement therapy.
There are no data indicating that dose adjustment is necessary in patients with hepatic impairment.
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).
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):
< 40 weeks)
100 mg/kg BW in 2 divided doses
200 mg/kg BW in 3 divided doses
Infants 1–12 months
(up to 10 kg BW)
mg/kg BW in 3 divided doses
Infants and children aged 1–12 years
(10–40 kg BW)
mg/kg BW in 3–4 divided doses
Sum of gestational and postnatal age.
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
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
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
- Hypersensitivity to the active substance, fosfomycin, or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Consideration should be given to co-administering intravenous fosfomycin with another antibacterial
agent, taking into account the remaining susceptibilities of the pathogen(s) under treatment. As it is
unknown whether the development of resistance to intravenous fosfomycin is higher when it is used as a
monotherapy, co-administration with other antibacterials should also be considered in order to prevent the
emergence of resistance.
1 g fosfomycin (equivalent to 1.32 g disodium fosfomycin) contains 14 mmol (320 mg) sodium. One
bottle with 2 g of fosfomycin contains 28 mmol (640 mg) sodium, one bottle with 4 g fosfomycin
contains 56 mmol (1280 mg) sodium and one bottle with 8 g of fosfomycin contains 111 mmol (2560 mg)
A high sodium load associated with the use of fosfomycin may result in decreased levels of potassium in
serum or plasma. A low-sodium diet is recommended during treatment. The substitution of potassium
may be necessary in some cases. Serum electrolyte levels and water balance must be monitored during
therapy. Caution is advised when fosfomycin is used in patients with cardiac insufficiency, hypertension,
hyperaldosteronism, hypernatraemia or pulmonary oedema.
Acute, potentially life-threatening hypersensitivity reactions (anaphylactic shock) may occur in very rare
cases. At the first signs (including sweating, nausea, cyanosis), the infusion of fosfomycin must be
immediately discontinued. The intravenous line should be left in place. Depending upon the clinical
situation, appropriate emergency measures may need to be initiated.
Antibacterial agent-associated colitis and pseudo-membranous colitis have been reported with nearly all
antibacterial agents including fosfomycin, and may range in severity from mild to life-threatening.
Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or
subsequent to the administration of fosfomycin. Discontinuation of therapy with fosfomycin and the
administration of specific treatment for Clostridium difficile should be considered. Medicinal products
that inhibit peristalsis should not be given.
In patients with severe renal insufficiency (creatinine clearance ≤ 40ml/min), the elimination of
fosfomycin is substantially slowed. See section 4.2 for appropriate dosing of fosfomycin in renal
4.5 Interaction with other medicinal products and other forms of interaction
No drug-drug interaction studies have been performed with fosfomycin. To date, no clinically relevant
pharmacological interactions between fosfomycin and other agents (drugs, stimulants or foodstuffs) have
Combination with other antibiotics
In-vitro tests have shown that the combination of fosfomycin with a β-lactam antibiotic such as penicillin,
ampicillin, cefazolin or the class of carbapenems, usually shows an additive to synergistic effect. The
same applies to the combination of fosfomycin with most anti-staphylococcal (linezolid,
quinupristin/dalfopristin, moxifloxacin) agents in the treatment of staphylococcal infections. The
combination of fosfomycin with aminoglycosides has predominantly indifferent to additive effects.
4.6 Fertility, pregnancy and lactation
To date, in humans no reduction in fertility after therapy with fosfomycin has been reported. In male and
female rats, reduced fertility was observed after the oral administration of fosfomycin at supra-therapeutic
doses (see section 5.3.).
For fosfomycin, no clinical data on pregnancies are available. Animal studies do not indicate direct or
indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal
development (see section 5.3). Fosfomycin should therefore not be prescribed to pregnant women unless
the benefit outweighs the risk.
After the administration of fosfomycin, low quantities of fosfomycin were found in human milk.
Fosfomycin should therefore not be administered during lactation, unless the benefit outweighs the risk.
4.7 Effects on ability to drive and use machines
Occasionally, even if the product is correctly administered, side effects may occur which impair the
ability to drive and use machines (see also section 4.8).
4.8 Undesirable effects
Summary of the safety profile
The most commonly reported adverse reactions during treatment are gastrointestinal disturbances and
injection site reactions. Other important adverse reactions include hypokalaemia and/or hypernatraemia.
Tabulated list of adverse reactions
Undesirable effects are listed by body system and frequency in accordance with the following
≥ 1/100 to < 1/10
≥ 1/1,000 to < 1/100
≥ 1/10,000 to < 1/1,000
cannot be estimated from the available data
System Organ Class
Adverse Drug Reactions
Blood and lymphatic
Aplastic anaemia, eosinophilia
Agranulocytosis, granulocytopenia, leucopenia,
pancytopenia, thrombocytopenia, neutropenia
Anaphylactic shock (see section 4.4)
Decreased appetite, hypernatraemia and/or hypokalaemia
(see section 4.4), oedema
Ear and labyrinth
Retching, stomach ache
Nausea, vomiting, diarrhoea
Pseudomembranous colitis (see section 4.4)
Blood alkaline phosphatase, aspartate aminotransferase and
alanine aminotransferase increased (transient)
Fatty liver (completely reversible after discontinuation of
Hepatitis, cholestatic hepatitis, icterus
Skin and subcutaneous
Angioedema, facial oedema, pruritus, urticaria
General disorders and
Injection site phlebitis
Description of selected adverse reactions
Hypokalaemia may result in diffuse symptoms such as weakness, tiredness or oedema and/or muscle
twitching. Severe forms may cause hyporeflexia and cardiac arrhythmia. Hypernatraemia may be
associated with hypertension and signs of fluid overload such as oedema (see section 4.4).
Limited safety information is available from the paediatric population. Frequency, type and severity of
adverse reactions may be expected to be similar to the adult population.
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 Yellow Card Scheme at:
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.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: antibiotics for systemic use, other antibacterials
Mode 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).
Pharmacokinetic (PK)/pharmacodynamic (PD) relationship
Limited data indicate that fosfomycin most likely acts in a time-dependent manner.
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.
The mode of action of fosfomycin differs from that of all other antibiotic classes. Fosfomycin was
generally found to be active in-vitro against clinical isolates of methicillin-resistant staphylococci,
vancomycin-resistant enterococci, penicillin- and erythromycin-resistant streptococci and multiresistant
Antimicrobial spectrum of fosfomycin (in vitro)
The data predict only the probability of micro-organism susceptibility to fosfomycin.
For intravenous fosfomycin, the susceptibility breakpoints established by the European Committee on
Antimicrobial Susceptibility Testing are as follows (EUCAST breakpoint table version 5.0, 2015):
≤ 32 mg/l
> 32 mg/l
≤ 32 mg/l
> 32 mg/l
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.
In-vitro activity spectrum of fosfomycin and resistance
The following table is based on the breakpoint according to EUCAST and comprises organisms relevant
for the approved indications:
Commonly susceptible species
Aerobic Gram-positive microorganisms
Aerobic Gram-negative microorganisms
Species in which acquired resistance may be a problem
Inherently resistant species
The physiologically important apathogenic anaerobic species, Lactobacillus and Bifidobacterium, are not
susceptible to fosfomycin.
5.2 Pharmacokinetic properties
A single intravenous infusion of 4 g and 8 g of fosfomycin in young healthy males resulted in maximum
serum concentrations (C
) of approx. 200 and 400 μg/ml, respectively. The serum half-life was approx.
2 hours. In elderly and/or critically ill male and female subjects, single intravenous doses of 8 g of
fosfomycin resulted in mean C
and half-lives in plasma of approximately 350–380 µg/ml and 3.6–3.8
The apparent volume of distribution of fosfomycin is approx. 0.30 l/kg body weight. Fosfomycin is
distributed well to tissues. High concentrations are reached in eyes, bones, wound secretions,
musculature, cutis, subcutis, lungs and bile. In patients with inflamed meninges, cerebrospinal fluid
concentrations reach approx. 20–50% of the corresponding serum levels. Fosfomycin passes the placental
barrier. Low quantities were found in human milk (about 8 % of the serum concentrations). The plasma
protein binding is negligible.
Fosfomycin is not metabolised by the liver and does not undergo enterohepatic circulation. No
accumulation is therefore to be expected in patients with hepatic impairment.
80–90% of the quantity of fosfomycin administered to healthy adults is eliminated renally within 10 hours
after a single intravenous administration. Fosfomycin is not metabolised, i.e. the biologically active
compound is eliminated. In patients with normal or mildly to moderately impaired renal function
(creatinine clearance ≥ 40 ml/min), approximately 50–60% of the overall dose is excreted within the first
Fosfomycin shows linear pharmacokinetic behaviour after intravenous infusion of therapeutically used
Very limited data are available in special populations.
No dose adjustment is necessary based on age alone. However, renal function should be assessed and the
dose should be reduced if there is evidence of renal impairment (see section 4.2).
The pharmacokinetics of fosfomycin in children and adolescents aged 3–15 years as well as in term
newborns with normal renal function are generally similar to those of healthy adult subjects. However, in
renally healthy neonates and infants up to 12 months, the glomerular filtration rate is physiologically
decreased compared to older children and adults. This is associated with a prolongation of the elimination
half-life of fosfomycin in dependence on the stage of renal maturation.
In patients with impaired renal function, the elimination half-life is increased proportionally to the degree
of renal insufficiency. Patients with creatinine clearance values of 40 ml/min or less require dose
adjustments (see also section 4.2. “Dosage in renal insufficiency” for further details).
In a study investigating 12 patients under CVVHF customary polyethylene sulfone haemofilters with a
membrane surface of 1.2 m
and a mean ultrafiltration rate of 25 ml/min were employed. In this clinical
setting, the mean values of plasma clearance and elimination half-life in plasma were 100 ml/min, and
There is no requirement for dosage adjustments in patients with hepatic insufficiency since the
pharmacokinetics of fosfomycin remains unaffected in this patient group.
5.3 Preclinical safety data
Subacute and chronic toxicity
The toxicity of fosfomycin following repeated administration for up to 6 months was evaluated in rats,
dogs, rabbits and monkeys. At high intra-peritoneal doses of fosfomycin (> 500 mg/kg /day), rats
developed respiratory arrest, tetanic cramps, anaemia, a reduction of blood protein levels, increased serum
cholesterol and reduced blood glucose. Furthermore, dogs and monkeys experienced diarrhoea due to
antibiotic-related changes in the intestinal flora following intravenous administration of doses of higher
than 250 mg/kg /day and 500 mg/kg /day, respectively. In the rabbit, no toxicity was observed following
intravenous administration of 400 mg/kg /day for a period of 1 month.
In male and female rats, following repeated administration (via a pharyngeal tube) of up to 1400 mg/kg
/day reduced fertility was observed at the maximum dose tested.
Fosfomycin was administered to mice, rats and rabbits via pharyngeal tube at maximum doses of 2 x 120
mg/kg /day, 1400 mg/kg /day and 420 mg/kg /day, respectively or intravenously to mice and rabbits at
55.3 mg/kg /day, and up to 250 mg/kg /day, respectively. There was no evidence of embryotoxicity or
Perinatal and postnatal toxicity
In rats, a maximum dose of 2800 mg/kg /day was administered via a pharyngeal tube. There was no
evidence of foetal or peri- and postnatal toxicity.
In-vitro tests were performed to test the alkylating capacity and the mutagenic effect of fosfomycin.
Fosfomycin showed no alkylating effect. In the Ames test, no mutagenic effect was seen in test strains of
Salmonella typhimurium (TA 98, TA 100, TA 1535, TA 1537 and TA 1538, with and without addition of
rat-liver homogenate) after exposure to fosfomycin at up to 1600 µg/ml.
6. Pharmaceutical particulars
6.1 List of excipients
Although no chemical/pharmaceutical incompatibilities have been found, Fomicyt solutions should not be
mixed together with other parenteral preparations with the exception of those listed in section 6.6.
6.3 Shelf life
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
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
For storage of the reconstituted solution see section 6.3.
6.5 Nature and contents of container
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
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
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.
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.
7. Marketing authorisation holder
INFECTOPHARM Arzneimittel und Consilium GmbH
Nordic Pharma UK Ltd
1650 Arlington Business Park
8. Marketing authorisation number(s)
9. Date of first authorisation/renewal of the authorisation
10. Date of revision of the text
Company Contact Details
Nordic Pharma Limited
3 Commerce Park, Brunel Road, Theale, Reading, Berkshire, RG7 4AB
+44 (0) 118 207 9161
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