Fosfomycin Sodium IV infusion is indicated for the treatment of the following infections in adults and children, including neonates:

• Osteomyelitis
• Complicated urinary tract infections
• Hospital-acquired lower respiratory tract infections
• Bacterial meningitis
• Bacteremia associated with, or suspected to be related to, any of the above infections

Fosfomycin should be reserved for use when standard first-line antibacterial agents are not suitable, or when alternative treatments have failed to show adequate effectiveness.

Fosfomycin exerts a bactericidal effect on actively proliferating pathogens by preventing the enzymatic synthesis of the bacterial cell wall. It inhibits the first stage of intracellular bacterial cell wall synthesis by blocking peptidoglycan formation.

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:

• Osteomyelitis: 12-24 gm in 2-3 divided doses
• Complicated urinary tract infection: 12-16 gm in 3 divided dose
• Nosocomial lower respiratory tract infection: 12-24 gm in 2-3 divided dose
• Bacterial meningitis: 16-24 gm in 3-4 divided doses

Individual doses must not exceed 8 gm. 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: Special precaution should be exercised 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.

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.

Pediatric 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):

• 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 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

Method of administration: 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 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.

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.

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

Fosfomycin is contraindicated in patients with hypersensitivity to the active substance, fosfomycin, or to any of the excipients.

The most commonly reported adverse reactions during treatment include gastrointestinal disturbances and injection site reactions. Other important adverse reactions include hypokalaemia and/or hypernatraemia.

• To help reduce the potential development of cross-resistance, co-administration of Fosfomycin with other antibiotics is preferred.
• The high sodium load associated with fosfomycin use may lead to decreased potassium levels in serum or plasma. A low-sodium diet is recommended during treatment, and potassium supplementation may be necessary in some cases. Serum electrolyte levels and fluid balance should be monitored during therapy. Caution is advised when fosfomycin is used in patients with cardiac insufficiency, hypertension, hyperaldosteronism, hypernatraemia, or pulmonary edema.
• In very rare cases, acute and potentially life-threatening hypersensitivity reactions, including anaphylactic shock, may occur. At the first signs of such reactions, including sweating, nausea, or cyanosis, fosfomycin infusion must be stopped immediately.

No clinical data are available regarding the use of fosfomycin during pregnancy. Therefore, fosfomycin should not be prescribed to pregnant women unless the potential benefit outweighs the possible risk. After administration, small amounts of fosfomycin have been found in human breast milk. For this reason, fosfomycin should not be used during lactation unless the potential benefit outweighs the possible risk.

Experience with fosfomycin overdose is limited. Reported cases following parenteral use have included hypotonia, somnolence, electrolyte disturbances, thrombocytopenia, and hypoprothrombinemia.

Intracellular antibiotic

Store below 30°C. Protect from light and moisture. Keep out of the reach of children. After reconstitution with solvent, this medicine should be used immediately, or stored in a refrigerator at 2°C to 8°C, protected from light, for up to 24 hours.