Fosfomycin Sodium

Complicated UTI, Nosocomial lower respiratory tract infections, Osteomyelitis, Bone and joint infections, Bacterial meningitis, Bacteremia

Adult Intravenous Fosfomycin Sodium IV Infusion should be used only when commonly recommended antibiotics are inappropriate, or when these alternative antibacterial agents have failed to demonstrate efficacy. The general dosage guidelines for adults with estimated creatinine clearance > 80 mL/min Osteomyelitis, Bone and joint infections, Nosocomial lower respiratory tract infections, Bacteremia Adult: 12–24 g daily in 2–3 divided doses (use the high-dose regimen in severe infection suspected or known to be caused by less sensitive organisms) Maximum per dose 8 g Complicated urinary-tract infections Adult: 12–16 g daily in 2–3 divided doses (max. per dose 8 g) Bacterial meningitis Adult: 16–24 g daily in 3–4 divided doses (max. per dose 8 g), use the high-dose regimen in severe infection suspected or known to be caused by less sensitive organisms

Child > 12 years of age (> 40 kg) Intravenous Fosfomycin Sodium IV Infusion should be used only when commonly recommended antibiotics are inappropriate, or when these alternative antibacterial agents have failed to demonstrate efficacy. Osteomyelitis, Bone and joint infections, Nosocomial lower respiratory tract infections, Bacteremia Adult: 12–24 g daily in 2–3 divided doses (use the high-dose regimen in severe infection suspected or known to be caused by less sensitive organisms) Maximum per dose 8 g Complicated urinary-tract infections Adult: 12–16 g daily in 2–3 divided doses (max. per dose 8 g) Bacterial meningitis Adult: 16–24 g daily in 3–4 divided doses (max. per dose 8 g), use the high-dose regimen in severe infection suspected or known to be caused by less sensitive organisms 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): Premature neonates (age <40 weeks): 100 mg/kg BW in 2 divided doses Neonates (age 40-44 weeks): 200 mg/kg BW in 3 divided doses Infants 1-12 months (up to 10 kg BW): 200-300 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 The high-dose regimen (>300 mg/kg/day) 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

Renal Impairment 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. Use intravenous treatment with caution if eGFR 40–80 mL/minute/1.73m2 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 sodium must be adjusted to the degree of renal impairment. Dose titration should be based on creatinine clearance values. Daily dosage adjustment CrCl 40-80 mL/min: No daily dosage adjustment CrCl <40 mL/min: 70% (in 2–3 divided doses) CrCl <30 mL/min: 60% (in 2–3 divided doses) CrCl <20 mL/min: 40% (in 2–3 divided doses) CrCl <10 mL/min: 20% (in 1–2 divided doses) Dosage in patients undergoing renal replacement therapy Patients undergoing chronic intermittent dialysis (every 48 hours) should receive 2 g of Fosfomycin Sodium at the end of each dialysis session. During continuous venovenous hemofiltration (post-dilution CVVHF), Fosfomycin Sodium is effectively eliminated. Patients undergoing post-dilution CVVHF will not require any dose adjustment. No clinical data exist for intravenous Fosfomycin Sodium in patients undergoing pre-dilution CVVHF or other forms of renal replacement therapy.

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.

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

For intravenous infusion Fosfomycin Sodium is intended for intravenous administration. The duration of infusion should be at least 30 minutes for the 4 gm pack size. Use only clear solutions. Preparation of the solution for infusion: Fosfomycin Sodium must be reconstituted and diluted prior to administration. Water for Injections and Glucose Infusion 50 mg/ml (5%) or Glucose Infusion 100 mg/ml (10%) may be used as a solvent for the reconstitution and dilution. Sodium Chloride containing solvents must not be used. Reconstitution: Shake the vial prior to the reconstitution to loosen up the powder. Reconstitute the 4 gm vials with 20 ml of solvent. Shake well to dissolve. A slight degree of warming occurs when the powder is dissolved. Dilution: Transfer the reconstituted contents of 4 gm vials into an infusion container with further 80 ml of solvent. The resulting solution for infusion is clear and colorless to slightly yellowish.

Hypersensitivity to the active substance, fosfomycin, or to any of the excipients.

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. To avoid the potential development of cross-resistance, co-administration of Fosfomycin with other antibiotics is preferred. 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 edema. MONITORING PARAMETERS With intravenous use: Monitor electrolytes and fluid balance.

Not Classi PREGNANCY No clinical data on pregnancies are available. Fosfomycin should therefore not be prescribed to pregnant women unless the benefit outweighs the risk. LACTATION 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.

No drug-drug interaction studies have been performed with fosfomycin.

GENERAL SIDE-EFFECTS Common or very common: Abdominal pain. diarrhoea. headache. nausea. vomiting Uncommon: Skin reactions Frequency not known: Antibiotic-associated colitis SPECIFIC SIDE-EFFECTS Uncommon With parenteral use: Appetite decreased. dyspnoea. electrolyte imbalance. fatigue. oedema. taste altered. vertigo Rare or very rare With parenteral use: Bone marrow disorders. eosinophilia. hepatic disorders. visual impairment Frequency not known With parenteral use: Agranulocytosis. asthmatic attack. confusion. leucopenia. neutropenia. tachycardia. thrombocytopenia

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).