⚠️ Warnings
Risk of resistance selection and need for combination therapy
In vitro, rapid selection of resistant mutants has been observed with fosfomycin. Intravenous administration of fosfomycin as monotherapy has also been associated with resistance selection in clinical studies. Therefore, whenever possible, fosfomycin should be administered as part of a combination antibacterial treatment regimen to reduce the risk of resistance selection.
Limited clinical data
Due to the lack of adequate randomised controlled clinical trials, only limited clinical data are available supporting the intravenous use of fosfomycin for some of the stated indications. Moreover, different dosing regimens have been used and clinical trial data do not adequately support any particular intravenous dosing regimen. Fosfomycin should be selected for the treatment of the stated indications only when the use of antibacterial agents commonly recommended for initial treatment of such infections is considered inappropriate.
Hypersensitivity reactions
Severe and sometimes fatal hypersensitivity reactions, e.g. anaphylaxis or anaphylactic shock, may occur during treatment with fosfomycin (see sections 4.3 and 4.8). If such reactions occur, treatment with fosfomycin must be discontinued immediately and appropriate emergency measures must be initiated.
Clostridioides difficile-associated diarrhoea
Clostridioides difficile-associated colitis and pseudomembranous colitis have been reported with fosfomycin, and their severity may range from mild to life-threatening (see section 4.8). It is therefore important to consider this diagnosis in patients who develop diarrhoea during or after administration of fosfomycin. Discontinuation of fosfomycin therapy and specific treatment against Clostridioides difficile should be considered. Medicinal products that inhibit peristalsis should not be administered.
Sodium and potassium levels and risk of sodium overload
Sodium and potassium levels must be monitored regularly in patients receiving fosfomycin, particularly during long-term treatment. Given the high sodium content (0.32 grams) per gram of fosfomycin, the risk of hypernatraemia and fluid overload must be assessed before initiating treatment, especially in patients with a history of congestive heart failure or related comorbidities such as nephrotic syndrome, hepatic cirrhosis, hypertension, hyperaldosteronism, pulmonary oedema or hypoalbuminaemia, as well as in neonates with sodium intake restriction. A low-sodium diet is recommended during treatment. Prolongation of the infusion and/or reduction of the individual dose (with more frequent administration) may also be considered. Fosfomycin may decrease serum or plasma potassium levels; therefore, potassium supplementation should always be considered.
Haematological reactions (including agranulocytosis)
Haematological reactions including neutropenia or agranulocytosis have occurred in patients receiving intravenous fosfomycin (see section 4.8). Therefore, white blood cell counts must be monitored at regular intervals and appropriate treatment must be initiated if such reactions occur.
Renal impairment
In patients with renal impairment, the dose should be adjusted according to the degree of renal impairment (see section 4.2).
Excipients
One gram of fosfomycin (equivalent to 1.32 g of fosfomycin disodium) contains 14 mmol (320 mg) of sodium, equivalent to 16% of the WHO recommended maximum daily dietary sodium intake for an adult of 2 g sodium. One 2 g vial of fosfomycin contains 28 mmol (640 mg) of sodium, one 4 g vial of fosfomycin contains 56 mmol (1,280 mg) of sodium and one 8 g vial of fosfomycin contains 111 mmol (2,560 mg) of sodium.
