FOMICYT

Posology 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):

The general dosage guidelines for adults and adolescents with estimated creatinine clearance > 80 ml/min are as follows: Table 1 – dosing in adults and adolescents with CrCl >80 ml/min Indication Daily dose Complicated urinary tract infection 12–24 g a in 2–3 divided doses Infective endocarditis 12–24 g a in 2–3 divided doses Bone and joint infections 12–24 g a in 2–3 divided doses Hospital-acquired pneumonia, including ventilator-associated pneumonia 12–24 g a in 2–3 divided doses Complicated skin and soft tissue infections 12–24 g a in 2–3 divided doses Bacterial meningitis 16–24 g a in 3–4 divided doses Complicated intra-abdominal infections 12–24 g a in 2–3 divided doses Bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above 12–24 g a in 2–3 divided doses 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.

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. 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). Renal impairment No dose adjustment is recommended in patients within estimated creatinine clearance between 40–80 ml/min.

However, 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. 083 20% (in 1-2 divided doses) 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 as calculated according to Cockgroft-Gault formula.

The first dose (loading dose) should be increased by 100%, 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. 2). Hepatic impairment No dose adjustment is necessary in patients with hepatic impairment. 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): Table 3 – Dosing in children and neonates Age/weight Daily dose Premature neonates (age a <40 weeks) 100 mg/kg BW in 2 divided doses Neonates (age a 40-44 weeks) 200 mg/kg BW in 3 divided doses Infants 1-12 months (up to 10 kg BW) 200-300 b mg/kg BW in 3 divided doses Infants and children aged 1≤12 years (10≤40 kg BW) 200-400 b mg/kg BW in 3-4 divided doses 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 of administration Fomicyt is intended for intravenous use. 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.

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. 6.

4), injection site reactions, dysgeusia and gastrointestinal disturbances. 4). Tabulated list of adverse reactions 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 from the available data Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

4) Uncommon Blood alkaline phosphatase increased (transient), Transaminases increased (ALAT, ASAT), gamma- GT increased Hepatobiliary disorders Not known Hepatitis Common Erythematous eruption Uncommon Rash Skin and subcutaneous tissue disorders Not known Angioedema, pruritus, urticaria Common Injection site phlebitisGeneral disorders and administration site conditions Uncommon Asthenia * see section below (Description of selected adverse reactions) Description of selected adverse reactions: Hypokalemia may result in diffuse symptoms such as weakness, tiredness or oedema and/or muscle twitching.

Severe forms may cause hyporeflexia and cardiac arrhythmia. 4). Severe forms may cause confusion, hyperreflexia, seizures and coma. Paediatric population 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 reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Risk of selecting for resistance and the need for combination therapy In vitro, fosfomycin has been found to rapidly select for resistant mutants. Also, the use of intravenous fosfomycin alone has been associated with selection of resistance in clinical studies.

Whenever possible, it is recommended that fosfomycin is administered as part of a combination antibacterial drug regimen to reduce the risk of selecting for resistance. Limitations of the clinical data The clinical data to support the use of intravenous fosfomycin for treatment of some of the listed indications is limited by a lack of adequate randomised controlled trials.

Furthermore, various dose regimens have been used and no single intravenous dose regimen has been strongly supported by clinical trial data. It is recommended that fosfomycin is selected to treat the listed indications only when it is considered inappropriate to use antibacterial agents that are commonly recommended for their initial treatment.

8). If such reactions occur, treatment with fosfomycin must be discontinued immediately and adequate emergency measures must be initiated. 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. Sodium and potassium levels and risk of sodium overload Sodium and potassium levels should be monitored regularly in patients receiving fosfomycin, in particular during prolonged treatment.

32 grams) per gram of fosfomycin, the risk of hypernatraemia and fluid overload should be assessed before starting treatment, especially in patients with a history of congestive heart failure or underlying comorbidities such as nephrotic syndrome, liver cirrhosis, hypertension, hyperaldosteronism, pulmonary oedema or hypoalbuminemia as well as in neonates under sodium restriction.

A low-sodium diet is recommended during treatment. An increase in the infusion length and/or a reduction to the individual dose (with more frequent administration) could also be considered. Fosfomycin may decrease potassium levels in serum or plasma, therefore potassium supplementation should be always considered.

8). Therefore, the leukocyte count should be monitored at regular intervals and if such reactions occur, an adequate medical treatment should be initiated. 2). 32 g disodium fosfomycin) contains 14 mmol (320 mg) sodium, equivalent to 16 % of the WHO recommended maximum daily dietary intake of 2 g sodium for an adult.

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) sodium.

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