Monural, 3 g 2 pcs

Pharmacotherapeutic group

antibiotic

ATX code: J01XX01.

Pharmacological properties

Pharmacodynamics.

Monural® contains phosphomycin [mono (2-ammonium-2-hydroxymethyl-1,3-propanediol)(2R-cis)-(3-methyloxyranil) phosphonate], a broad spectrum antibacterial agent, a phosphonic acid derivative intended to treat urinary tract infections. The mechanism of action is associated with inhibition of the first stage of synthesis of the bacterial cell wall. Being a structural analogue of phosphoenolpyruvate it competitively inhibits irreversibly the enzyme UDF-N-acetylglucosamienolpyruviltransferase, which catalyzes the reaction of formation of UDF-N-acetyl-3-O-(1-carboxyvinyl)-B-glucosamine from phosphoenolpyruvate and UDF-N-acetyl-D-glucosamine.

The drug is also able to reduce bacterial adhesion to the bladder mucosa, which can play the role of a predisposing factor for recurrent infections. The mechanism of action of the drug explains the absence of cross-resistance with other antibiotics and the mutual enhancement of action with antibiotics of other classes, such as beta-lactam antibiotics.

Phosphomycin is active against a wide range of Gram-positive and Gram-negative microorganisms commonly isolated in urinary tract infections, such as Escherichia coli, Citrobacter spp., Klebsiella spp., Proteus spp., Serratia spp., Pseudomonas aeruginosa, Enterrococcus faecalis. The emergence of resistance under laboratory conditions is explained by mutations in the gIpT and uhp genes, which control L-alpha-glycerophosphate and glucose phosphate transport, respectively.

Pharmacokinetics.

Intake: When administered orally, phosphomycin is well absorbed from the intestine and achieves a bioavailability of about 50%. Maximum concentration in plasma is observed 2-2.5 hours after oral administration and is 22-32 mg/l. The plasma elimination half-life is 4 hours.

Ingestion with food slows absorption without affecting the concentration in the urine.

Distribution: Fosfomycin is distributed in the kidneys, bladder wall, prostate and seminal glands. A steady urinary concentration of fosfomycin exceeding the Minimum Bacteriostatic Concentration (MBc) is reached 24-48 hours after oral administration.

Phosphomycin does not bind to plasma proteins and crosses the placental barrier.

Fosfomycin is excreted into breast milk in small amounts after a single injection.

Elimation: Fosfomycin is excreted unchanged mainly by the kidneys through glomerular filtration (40-50% of the dose taken is found in the urine), with a half-life of about 4 hours, and to a lesser extent in the feces (18-28% of the dose). The occurrence of a second peak serum concentration 6 and 10 hours after drug administration suggests that the drug is subject to intestinal hepatic recirculation.

The pharmacokinetic properties of fosfomycin are independent of age and pregnancy. The drug cumulates in patients with renal insufficiency; a linear relationship between pharmacokinetic parameters of fosfomycin and glomerular filtration rate has been established.

Indications

Active ingredient

Composition

Active ingredient:

Phosphomycin trometamol;

Associates:

Tangerine flavoring;

Orange flavoring;

saccharin;

saccharose

How to take, the dosage

Ingestion.

The granules are dissolved in 1/2 cup of water (50-75 ml) or other beverage, stirred until completely dissolved, taken immediately after dissolution. Monural® is taken once a day orally on an empty stomach 1 hour before or 2-3 hours after a meal, preferably before going to bed, having previously emptied the bladder.

Adults and children from 12 to 18 years: 1 sachet (3 g) once a day.

In order to prevent urinary tract infection during surgical interventions and transurethral diagnostic procedures Monural® is taken 2 times in 3 g: 3 hours before and 24 hours after the intervention.

In children from 5 to 12 years of age: 1 sachet (2 g) once a day. In order to prevent infection of the urinary tract in case of surgical operations and transurethral diagnostic procedures Monural® is taken 2 g 2 times: 3 hours before the operation and 24 hours after the operation.
In more severe cases (elderly patients, recurrent infections) one more sachet is taken after 24 hours.

In patients with mild to moderate renal insufficiency no dose adjustment is required. In patients with severe renal failure or those on hemodialysis the use of the drug is contraindicated. No dose adjustment is required in patients with hepatic impairment.

Interaction

Metoclopramide. When concomitant use of fosfomycin and metoclopramide, which increases gastrointestinal motility, the concentration of fosfomycin in blood serum and its excretion in the urine are reduced. Other drugs that increase gastrointestinal motility may have a similar effect.

Probenecid. Probenecid should not be administered concomitantly with fosfomycin, because it has been proven to significantly reduce renal clearance and excretion of fosfomycin.

Probenecid when administered to healthy volunteers receiving fosfomycin infusion significantly decreased renal clearance, probably by inhibiting tubular secretion, resulting in lower urinary concentrations of the drug.

Therapeutic evaluation of the effects of metoclopramide and probenecid on urinary fosfomycin levels after their combined use with fosfomycin in women with acute urinary tract infection has not been performed. Based on data obtained in healthy volunteers, urinary concentrations of phosphomycin cannot exceed the bactericidal concentration for a long enough period of time to lead to a microbiological cure. None of these drugs should be administered concomitantly with fosfomycin.

Cimetidine. Cimetidine does not affect the pharmacokinetics or urinary concentrations of phosphomycin when used together.

Eating. Food intake delays the absorption of phosphomycin, which leads to a decrease in plasma Cmax and urinary concentrations. Therefore, it is recommended that fosfomycin tromethamine be taken on an empty stomach or at least 2-3 h after a meal.

Special Instructions

Hypersensitivity reactions may occur during treatment with fosfomycin, including anaphylaxis and anaphylactic shock, which are life-threatening. If such a reaction occurs, repeated administration of fosfomycin should be ruled out and adequate treatment should be given.

Antibiotic-associated diarrhea has been reported with virtually all antibacterial agents, including fosfomycin. Its severity can range from mild diarrhea to fatal colitis. Diarrhea, especially severe, persistent and/or bloody diarrhea during or after treatment with Monural® (including for several weeks after treatment) may be a symptom of a disease caused by Clostridium difficile (pseudomembranous colitis). This diagnosis is important to consider when treating patients during or after taking Monural®. If the diagnosis of pseudomembranous colitis is suspected or confirmed, appropriate treatment should be started immediately. Drugs that inhibit intestinal peristalsis are contraindicated in this clinical situation.

Renal insufficiency: urinary concentrations of phosphomycin persist for 48 hours after the usual dose if creatinine clearance is greater than 10 ml/min.

The drug is contraindicated in patients undergoing hemodialysis.

Patients with diabetes should note that 1 packet of Monural® with a dosage of 2 g or 3 g of phosphomycin contains 2.100 g or 2.213 g of sucrose, respectively.

Patients with rare hereditary diseases such as fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase deficiency are contraindicated with this drug.

Contraindications

Side effects

In three U.S. studies, 1,233 patients received therapy with fosfomycin. The most frequent adverse reactions that occurred in >1% of patients, regardless of association with drug use, were diarrhea (10.4%), headache (10.3%), vaginitis (7.6%), nausea (5.2%), rhinitis (4.5%) back pain (3.0%), dysmenorrhea (2.6%), pharyngitis (2.5%), dizziness (2.3%), abdominal pain (2.2%), pain (2.2%), dyspepsia (1.8%), asthenia (1.7%) and rash (1.4%).

In addition, the following adverse reactions were observed with a frequency of less than 1%: Stool disorders, anorexia, constipation, dry mouth, dysuria, hearing loss, fever, flatulence, flu-like syndrome, hematuria, infections, insomnia, lymphadenopathy, menstrual disorders, migraine, myalgia, nervousness, paresthesia, itching, skin conditions (skin disorders) and vomiting.

In the U.S. study population, statistically significant laboratory changes reported without drug association included increased eosinophil counts, increased or decreased white blood cell counts, increased bilirubin, ALT and AST levels, ALP, decreased hematocrit, Hb levels, and increased and decreased platelet counts. The changes were usually transient, clinically insignificant, and occurred in less than 1% of patients.

In the same population, there have been studies of adverse adverse reactions that were considered associated with fosfomycin administration and occurred in more than 1% of patients receiving fosfomycin. They included diarrhea (9%), vaginitis (5.5%), nausea (4.1%), headache (3.9%), dizziness (1.3%), asthenia (1.1%), and dyspepsia (1.1%). The most frequently observed reaction, diarrhea, was considered mild and transient (passed without any intervention).

One case of unilateral optic neuritis has been reported and was considered probably associated with fosfomycin use.

In the post-registration period of fosfomycin use, there have been reports of vulvovaginitis, tachycardia, hearing impairment, urticaria and anaphylactic reactions, including anaphylactic shock and hypersensitivity. Cases of angioedema, aplastic anemia, asthma (exacerbation), cholestatic jaundice, general decreased taste sensation, hepatic necrosis, metallic taste in the mouth, and vestibular disorders have also been reported. One case of toxic megacolon has been reported and was found to be unrelated to phosphomycin administration.

Overdose

The data on fosfomycin overdose with oral administration are limited.

Symptoms: in cases of overdose during parenteral use hypotension, somnolence, disorders of water-electrolyte balance, thrombocytopenia and hypoprothrombinemia have been reported.

Treatment: in case of overdose symptomatic and supportive therapy should be carried out. Excretion of fosfomycin with urine should be stimulated by adequate fluid intake.

Pregnancy use

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