Exelfos

White granules with fruit flavor (orange-mandarin).
Fosfomycin 3 g (equivalent to fosfomycin trometamol 5.631 g).

ATC Code: J01XX01. Other antibacterials.
Pharmacology: Pharmacodynamics: Mechanism of action: Fosfomycin trometamol is an antibiotic with a broad spectrum of activity, derivate from phosphonic acid.
Fosfomycin bactericidal effect consists in block wall cellular synthesis. The specific mechanism inhibiting enolpyruvyl transferase avoid cross resistances with other antibiotics.
Relationship between pharmacokinetics and pharmacodynamics: Relationship between pharmacokinetics and pharmacodynamics of Fosfomycin trometamol has not been established.
The drug activity depends substantially on the period when the concentration of the active ingredient is above the minimum inhibitory concentration (MIC) of the bacterial agent.
Mechanisms of resistance: A resistance to fosfomycin can be based on the following mechanisms: Fosfomycin is admitted into the bacterial cell actively via two different transport systems (glycerin-3-phosphate and hexose-6 transport system). In Enterobacteriaceae the glycerin-3-phosphate transport system can be changed in such a way that fosfomycin is no longer transported into the cell.
Another plasmid-encoded mechanism occurring in Enterobacteriaceae, Pseudomonas spp. and Acinetobacter spp. is based on the presence of a specific protein, under the effect of which fosfomycin metabolises and is bound to glutathione (GSH).
In staphylococci a plasmid-encoded fosfomycin resistance also occurs. The exact mechanism of the resistance has not yet been determined.
A cross-resistance of fosfomycin with other antibiotics classes is not known.
Limit values: The testing of fosfomycin is performed using the routine dilution series. The evaluation of the results is performed on the basis of the limit values for fosfomycin. The following minimum inhibitory concentrations for susceptible and resistant germs were established: See table.

Click on icon to see table/diagram/image

Microbiological sensibility: Fosfomycin is active in front of Gram-positive and Gram-negative microorganisms strain penicillinases producers included, and usual urinary pathogen agents like Escherichia coli, Proteus, Klebsiella, Enterobacter, Staphylococcus, Streptococcus, and other resistant strains.
Organisms intrinsically resistant: S. saprophyticus.
Pharmacokinetics: Absorption: Fosfomycin trometamol is well absorbed by oral administration, achieving therapeutic urinary concentrations until 36 hours after single dose.
Distribution: After administration of 2 or 3 g of fosfomycin it is obtained the following plasmatic concentration 20-30 mcg/ml.
Elimination: Fosfomycin is excreted unchanged mainly into the urine. High urinary levels (about 3000 mcg/ml) are rapidly reached within 2-4 hours, and last for at least 36 hours.
In patients with moderately reduced renal function (Creatinine clearance - CrCl <80 ml/min), including the physiological reduction in the elderly, the half-life of fosfomycin is slightly prolonged but urinary concentration remains therapeutically adequate.
Toxicology: Preclinical safety data: Fosfomycin trometamol potential toxic effect does not differ from calcium and sodium fosfomycin.
There is no evidence that fosfomycin has teratogenic effect in different animal species, neither in fertility studies.
Fosfomycin trometamol mutagenic and carcinogenic studies have negative results.

Acute bacterial cystitis, acute episodes of recurrent bacterial cystitis, acute bacterial urethro-vesical syndrome, aspecific bacterial urethritis.
Relevant asymptomatic bacteriuria (pregnancy).
Post-operative urinary tract infections.
Prophylaxis of urinary tract infections during surgery and trans-urethral diagnostic maneuvers.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Adults: In acute, not complicated infections of the low urinary tract (cystitis, non-gonococcal urethritis) caused by germs susceptible to fosfomycin, one sachet of Fosfomycin (Exelfos) (3 grams) in a single daily administration.
In the prophylaxis of urinary infections after surgery or transurethral diagnostic maneuvers, the treatment should be applied usually with two doses of Fosfomycin (Exelfos). The first dose (1 sachet of 3 grams) is administered about 3 hours before surgery, the second dose (1 sachet of 3 grams) is administered 24 hours after the first one.
Elderly patients, other clinical situations: In elderly, bed-ridden patients, recurrent infections or infections by susceptible microorganisms to higher doses of antibiotic (Pseudomonas, Enterobacter, Proteus positive-indole) a second dose of fosfomycin trometamol could be necessary 24 hours after the first one.
Patients with renal insufficiency: For patients with mild to moderate renal insufficiency, dose adjustments are not needed. Fosfomycin (Exelfos) is not to be used in patients with severe renal insufficiency, neither during hemodialysis.
Method of administration: Fosfomycin trometamol is administrated as oral solution.
The contents of each sachet, of fosfomycin should be dissolved in half a glass of water (at least 50 mL) and drink it immediately preferably before the night resting, after voiding the bladder.

It is not described poisoning at therapeutical doses.
In the event of overdose, it is enough increase urinary elimination of drug substance by oral liquids administration.

Hypersensitivity to the active substance or to any of the excipients listed in Description.
Fosfomycin trometamol is contraindicated in: Patients with known hypersensitivity to the drug; Patients with severe renal insufficiency (Cl_cr <10 mL/min); Patients undergone haemodialysis; Children younger than 12 years old.

Hypersensitivity reactions, including anaphylaxis and anaphylactic shock, may occur during fosfomycin treatment and may be life-threatening (see Adverse Reactions). If such reaction occurs, fosfomycin should never be re-administrated and an adequate medical treatment is required. Before administering Fosfomycin (Exelfos), it is advisable to ask the patient about any previous manifestations of hypersensitivity to fosfomycin.
Clinical symptoms generally disappear in 2 or 3 days after treatment. The occasional persistence of some symptoms does not mean a therapeutic failure, it could probably be a consequence of the inflammation process.
Food delays oral absorption of fosfomycin trometamol, as consequence, fosfomycin trometamol administration is recommended on an empty stomach, 1 hour before of food ingestion or 2 hours after food ingestion.
Fosfomycin (Exelfos) contains sucrose. It is not recommended in patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency.
Effects on ability to drive and use machines: Not relevant.

Pregnancy: Several studies on animals with fosfomycin trometamol have not shown any evidence of damaging effects on the fetus. Previous studies in rats, sodium and calcium fosfomycin we could only detect toxic effects on fetus when using 25 times therapeutic dose. In rabbits the minimum dose doesn't show toxicity signs.
In spite of results of studies on animals with fosfomycin trometamol have not shown any teratogenic effect, and single dose administration in pregnancy reduce teratogenic risk compared with longer treatments, the administration is only recommended when the benefit/ risk balance is considered favourable.
Breastfeeding: Fosfomycin trometamol is excreted into milk during breastfeeding, in consequence, the administration is only recommended in breastfeeding when the benefit/risk balance is considered favourable.

The most common adverse reactions following the single-dose administration of fosfomycin trometamol involve the gastrointestinal tract, mainly diarrhoea. These events are usually self-limited in duration and resolve spontaneously.
The following table displays ADRs that have been reported with the use of fosfomycin from either clinical-trial or post-marketing experiences.
The displayed frequency categories use the following convention: Very common (1/10); Common (1/100 to < 1/10); Uncommon (1/1000 to < 1/100); Rare (1/10000 to < 1/1000); Very rare (< 1/10000); Not known (cannot be estimated from the available data).
Blood and lymphatic system disorders: Not known: slight increase of eosinophils and platelets count, with mild petechiae.
Rare: aplastic anemia.
Immune system disorders: Rare: hypersensitivity, exanthema, urticaria and angioedema, and severe anaphylactic reactions including anaphylactic shock (see Precautions).
Gastrointestinal disorders: Common: vomiting, diarrhoea, dyspepsia, nausea.
Hepatobiliary disorders: Not known: transient increase of plasmatic alkaline phosphates and aminotransferases.
Others: Not known: visual disturbances, lack of appetite, phlebitis, dyspnea, bronchospasm and cephalea.
Rare: superinfections from resistant bacteria.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

The concomitant administration of metoclopramide reduces the oral absorption of fosfomycin trometamol.
Food may delay the absorption of Fosfomycin trometamol (see Precautions).
Although no more cases of interaction have been reported, medicines that increase the movement of the stomach or intestines (like bethanechol, cisapride, domperidone and laxatives) may also reduce the effect of the antibiotic.

Incompatibilities: Not applicable.
Special precautions for disposal and other handling: No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

This medicinal product does not require any special storage conditions.
Single use only.
Store at temperatures not exceeding 30°C.

Other Antibiotics

J01XX01 - fosfomycin ; Belongs to the class of other antibacterials. Used in the systemic treatment of infections.

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