GRANULES FOR SOLUTION
Fosfomycin trometamol is a phosphonic acid derivative, which acts primarily by interfering with bacterial peptidoglycan synthesis, thereby disrupting cell wall synthesis. It has a broad spectrum of activity against aerobic bacteria, including those that cause UTIs.
Fosfomycin is a broad spectrum antibiotic that concentrates in kidney and bladder and is used to treat uncomplicated urinary tract infections. It is a phosphoenolpyruvate analogue produced by Streptomyces that irreversibly inhibits enolpyruvate transferase (MurA), which prevents the formation of N-acetylmuramic acid, an essential element of the peptidoglycan cell wall.
Absorption and Distribution
After a single oral dose of fosfomycin trometamol (3 g of fosfomycin) in healthy volunteers, mean peak plasma concentrations (Cmax) ranged from 22 to 32 mg/L and were reached betwee 2 to 2.5 hours (tmax) after administration. The oral bioavailability of a single dose of fosfomycin trometamol ranges from 34% to 41%, but this proportion increases tio 54 – 65% when expressed as a ration of the total oral dosage recovered in the urine.
Fosfomycin is distributed to the kidneys, bladder wall, prostate and seminal vesicles. Animal and in vitro pharmacodynamics studies have shown that fosfomycin has little or no effect on the CNS, cardiovascular, respiratory and gastrointestinal systems. Fosfomycin crosses the placental barrier, reaching therapeutic concentrations in the fetus.
Metabolism and Excretion
The mean terminal half-life of fosfomycin is 5.7 hours and is independent of the administered dose. Concomitant administration of food does not modify the achievement of bactericidal concentrations of the drug in the urine or its therapeutic efficacy. Fosfomycin is primarily excreted unchanged in the urine by glomerular filtration. The total body and renal clearances are quite similar; only 0.5% of fosfomycin is excreted by the biliary route. Since the total clearance of fosfomycin is equivalent to the glomerular filtration rate, tubular secretion and reabsorption probably do not occur. The percentage of an oral dose which is excreted in the urine 48 hours following administration ranges from 32% to 43%, of which about 85 – 95% is excreted in the first 24 hours. The mean peak of urinary concentrations of fosfomycin, with values ranging from 1053 to 4415 mg/L, was recovered in the 4 hours following the administration of a single oral dose.
Fosfomycin is essentially a urinary antibiotic. It is indicated for:
- Treatment of uncomplicated lower UTIs in adult
- Treatment of bacteriuria in pregnancy.
- Treatment of pediatric UTIs.
- Prophylaxis before urological procedures
- Treatment of pyelonephritis and complicated UTIs.
DOSAGE AND ADMINISTRATION
Fosfomycin is very well tolerated. It may be taken with or without food.
Fosfomycin should not be taken in its dry form. Fosfomycin should always be mixed with water prior to ingestion; hot water should not be used.
Fosfomycin trometamol is indicated for the treatment of lower uncomplicated UTI at a single oral dose of 3g.
The pharmacokinetics of fosfomycin in elderly patients showed only minor changes in some parameters, but on the whole they are substantially in agreement with those recorded in young healthy volunteers; thus, no dose adjustment is required with age.
In children, where fosfomycin is administered in mg/kg dosages, pharmacokinetic studies showed a significant correlation between the mg/kg dose and the obtained plasmatic Cmax. The proportion of the drug recovered in the urine in the intererval of 0-24 hours ranged from 44% to 58%, according to the administered dose.
The concomitant administration of metoclopramide significantly reduces the absorption of fosfomycin and it is therefore contraindicated.
WARNINGS AND PRECAUTIONS
No more than 1 single dose of fosfomycin should be used to treat a single episode of acute cystitis. Urine specimens for culture and susceptibility testing should be obtained before and after completion of therapy.
Safety and efficacy have not been established in pediatric patients less than 12 years of age. Fosfomycin is only approved for use in women 18 years of age and older.
In general, fosfomycin is well tolerated with minimal and transient adverse reactions. Adverse effects, if they occur, are usually short-lived due to the fact that fosfomycin is given as a single dose.
|Gastrointestinal||diarrhea (9%), nausea (4.1%), abdominal pain (2.2%), and dyspepsia (1.1%). Abnormal stools, anorexia, constipation, dry mouth, flatulence, vomiting, and toxic megacolon have been reported rarely.|
|headache (10%), dizziness (2.3%), asthenia (1.7%); paresthesia, migraine, somnolence, and nervousness|
|vaginitis (5.5%), dysmenorrhea (2.6%), dysuria, and menstrual disorder|
|Hematologic||rare reports of aplastic anemia. Transient laboratory changes have also been reported in trials: increased eosinophil count, increased or decreased WBC count, increased bilirubin, increased alkaline phosphatase, increased or decreased platelet counts, and decreased hemoglobin.|
|reported rarely and include cholestatic jaundice and hepatic necrosis. Transient increases in SGPT and SGOT|
Hypersensitivity reactions such as rash have been reported infrequently (less than 2%). One case of anaphylactic shock has been reported.
Fosfomycin does not adversely affect the pharmacological effects of widely prescribed drugs like analgesics, anticonvulsants, bronchodilators, diuretics, spasmolytics and antipyretics. At the same time, the use of these drug classes does not affect the efficacy of fosfomycin trometamol.
PREGNANCY AND LACTATION
Pregnancy Catergory B. Fosfomycin seems to be relatively safe for use during pregnancy. No significant fetotoxicity has been reported in studies of treatment of asymptomatic bacteriuria in pregnancy with fosfomycin.
3g/sachet Granules for Solution
Store at temperatures not exceeding 30°C.