Chemical formula: C₃H₇O₄P Molecular mass: 138.059 g/mol PubChem compound: 446987
Fosfomycin interacts in the following cases:
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 impairment.
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:
Creatinine clearance (CLCR) in men [ml/min]: (140-age [years]) x body weight [kg] / 72 x serum creatinine [mg/dl]
In order to calculate CLCR in women, the result of this formula is multiplied by 0.85.
Dosage table for patients with impaired renal function:
| CLCR patient | CLCR patient/CLCR normal | Daily dosage recommendeda |
|---|---|---|
| 40 ml/min | 0.333 | 70% (in 2–3 divided doses) |
| 30 ml/min | 0.250 | 60% (in 2–3 divided doses) |
| 20 ml/min | 0.167 | 40% (in 2–3 divided doses) |
| 10 ml/min | 0.083 | 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
The first dose should be increased by 100% (loading dose), but must not exceed 8 g.
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.
No clinical data exist for intravenous fosfomycin in patients undergoing pre-dilution CVVHF or other forms of renal replacement therapy.
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.
Concomitant administration of metoclopramide has been shown to lower serum and urinary concentrations of fosfomycin and should be avoided.
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.
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.
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.
At the present time, single-dose antibacterial treatments are not suitable to treat urinary tract infections in pregnant women.
However, for fosfomycin, animal studies do not indicate reproductive toxicity. A large amount of data concerning effectiveness of fosfomycin during pregnancy is available. Only moderate amount of safety data on pregnant women is available and does not indicate any malformative or foetal/neonatal toxicity of fosfomycin.
The use of fosfomycin may be considered during pregnancy, if necessary.
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. Fosfomycin should therefore not be prescribed to pregnant women unless the benefit outweighs the risk.
Fosfomycin is excreted into human milk at low level after a single injection. Therefore fosfomycin can be used during breastfeeding, after a single oral dose.
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.
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.
No specific studies have been performed but patients should be informed that dizziness has been reported. This may influence some patients' 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.
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