Fosforal Rompharm (Granules) Instructions for Use

Marketing Authorization Holder

S.C. Rompharm Company S.R.L. (Romania)

ATC Code

J01XX01 (Fosfomycin)

Active Substance

Fosfomycin (Rec.INN registered by WHO)

Dosage Form

Fosforal Rompharm

Granules for oral solution 3 g: sachets 8 g 1 or 2 pcs.

Dosage Form, Packaging, and Composition

Granules for oral solution from white to light yellow in color, with a lemon odor.

Excipients: calcium hydroxide – 0.3 g, lemon flavor – 0.2 g, sodium saccharin – 0.01 g, powdered sugar – up to 8 g.

8 g – multilayer laminated sachets (1) – cardboard packs.
8 g – multilayer laminated sachets (2) – cardboard packs.

Clinical-Pharmacological Group

Antibiotic of the phosphonic acid derivative group

Pharmacotherapeutic Group

Antibiotic

Pharmacological Action

Fosfomycin is a broad-spectrum antibiotic, a derivative of phosphonic acid. Its mechanism of action is associated with the suppression of the first stage of bacterial cell wall synthesis. Being a structural analogue of phosphoenolpyruvate, it competitively and irreversibly inhibits the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase, which catalyzes the reaction of UDP-N-acetyl-3-O-(1-carboxyvinyl)-D-glucosamine formation from phosphoenolpyruvate and UDP-N-acetyl-D-glucosamine.

Fosfomycin is also able to reduce the adhesion of bacteria to the mucous membranes of the bladder, which can play a role as a predisposing factor for recurrent infections.

Fosfomycin is active against gram-positive aerobes – Staphylococcus aureus, Staphylococcus epidermidis (including methicillin-resistant strains), Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis; gram-negative aerobes – Escherichia coli, Citrobacter spp., Enterobacter spp., Proteus mirabilis, Proteus vulgaris, Providencia (Proteus) rettgeri, Serratia marcescens, Haemophilus influenzae, Pseudomonas aeruginosa, Neisseria meningitidis, Neisseria gonorrhoeae, Salmonella spp., Shigella spp., Campylobacter spp., Yersinia enterocolitica.

Most strains of Klebsiella spp. and Providencia spp. are moderately sensitive to fosfomycin. Bacteroides spp., Brucella spp., Corynebacterium spp., Mycoplasma spp., Chlamydia spp., Treponema spp., Borrelia spp. and Mycobacterium spp. are resistant to fosfomycin.

Secondary resistance of microorganisms to fosfomycin rarely develops. There is no cross-resistance with other antibacterial agents. When combined with beta-lactams, fluoroquinolones, glycopeptides, or aminoglycosides, a pronounced synergy of antimicrobial action is noted against a wide range of gram-positive and gram-negative aerobic bacteria.

Pharmacokinetics

After oral administration, fosfomycin is well absorbed from the gastrointestinal tract; its bioavailability is about 50%. C_max in plasma is observed 2-2.5 hours after oral administration and is 22-32 mg/l. T_1/2 is 4 hours. After intravenous administration, T_1/2 is 1.7 hours.

Fosfomycin rapidly penetrates and is well distributed in many organs and tissues of the body. It does not bind to plasma proteins and is not metabolized. It crosses the placenta. It penetrates into breast milk in small concentrations. Fosfomycin is excreted primarily by the kidneys unchanged, creating high concentrations in the urine.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to fosfomycin.

For oral administration: acute bacterial cystitis, acute episodes of recurrent bacterial cystitis; bacterial nonspecific urethritis; asymptomatic massive bacteriuria in pregnant women; postoperative urinary tract infections. Prophylaxis of infections during surgical interventions on the urinary tract and during transurethral diagnostic examinations.

For parenteral administration: soft tissue infections, including in patients with peripheral circulation disorders (diabetes mellitus, diseases of the arteries of the lower extremities), burn wound infections; bone and joint infections; lower respiratory tract infections, including pneumonia and infections in patients with cystic fibrosis; intra-abdominal infections – acute cholecystitis, cholangitis, peritonitis; infectious and inflammatory diseases of the pelvic organs – salpingitis, endometritis, pelvic peritonitis; urinary tract infections, including acute and exacerbation of chronic pyelonephritis.

Fosfomycin can be used as part of combination therapy with antibiotics of other groups for the following diseases: CNS infections – bacterial meningitis, including postoperative; bacterial endocarditis; sepsis.

ICD codes

Dosage Regimen

Administer orally or intravenously. Determine the dose, route, and duration of therapy individually based on indication, infection severity, clinical status, patient age, and formulation.

For oral administration, use the granules for solution. Dissolve the entire contents of a single 3 g sachet in a glass of water. Stir thoroughly and ingest immediately. For acute bacterial cystitis, administer a single 3 g dose.

For recurrent cystitis, a single 3 g dose may be repeated every 48-72 hours. For perioperative prophylaxis in urological surgery or diagnostic procedures, administer a single 3 g dose 3 hours before the intervention.

For intravenous administration, calculate the dose based on patient weight and renal function. For adults with normal renal function, the typical dose is 2-4 g intravenously every 8 hours for severe systemic infections. For pediatric patients, administer 100-300 mg/kg/day intravenously, divided into 3-4 doses.

Adjust the dosage in patients with renal impairment. In mild to moderate impairment (CrCl 10-50 ml/min), reduce the dose or extend the dosing interval. Contraindicated in severe renal failure (CrCl <10 ml/min) and patients on hemodialysis.

Monitor liver and kidney function, electrolyte levels, and complete blood count during prolonged therapy. Discontinue treatment if severe diarrhea occurs, as it may indicate antibiotic-associated colitis.

Adverse Reactions

From the hematopoietic system: rarely – leukopenia, anemia, granulocytopenia, eosinophilia, pancytopenia, agranulocytosis or thrombocytopenia; very rarely – aplastic anemia.

From the immune system frequency unknown – anaphylactic shock, angioedema and other hypersensitivity reactions.

From the digestive system: often – dyspeptic symptoms; infrequently – nausea, vomiting, diarrhea; rarely – antibiotic-associated colitis, stomatitis.

From the skin and subcutaneous tissues rarely – rash, urticaria, itching, exanthema, pruritus.

From the liver and biliary tract : frequency unknown – short-term increase in alkaline phosphatase and liver transaminases activity.

Other rarely – feeling of fatigue.

When taken orally infrequently – vulvovaginitis; rarely – superinfection; infrequently – headache, dizziness, abdominal pain, vomiting; rarely – paresthesia; very rarely – tachycardia; frequency unknown – decreased blood pressure, petechiae, decreased appetite, shortness of breath, asthma, bronchospasm.

With parenteral use infrequently – thrombophlebitis, shortness of breath; rarely – hypernatremia, hypokalemia, electrolyte imbalance, palpitations, vascular pain, hyperemia, increased body temperature, pain at the injection site, cough, acute attack of bronchial asthma, chest discomfort, feeling of tightness in the chest, impaired renal function, edema, increased blood urea concentration, proteinuria, phlebitis, thirst, feeling of general malaise; frequency unknown – increased fatigue, confusion, convulsions.

Contraindications

Hypersensitivity to fosfomycin; severe renal failure (CrCl<10 ml/min), hemodialysis; childhood – depending on the dosage form.

Use in Pregnancy and Lactation

During pregnancy, use is possible only if the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

If it is necessary to use fosfomycin during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

During long-term therapy with fosfomycin, liver function should be periodically monitored.

Use in Renal Impairment

Use in patients with severe renal failure or on hemodialysis is contraindicated.

Pediatric Use

Use in children is possible according to indications, in age-appropriate recommended doses and dosage forms. It is necessary to strictly follow the instructions in the fosfomycin drug leaflets regarding contraindications for the use of specific fosfomycin dosage forms in children of different ages.

Geriatric Use

Fosfomycin is eliminated mainly through the kidneys. In elderly patients, it should be used with particular caution, as many patients in this category have reduced renal function, which leads to a greater likelihood of adverse reactions.

Special Precautions

During long-term therapy with fosfomycin, liver and kidney function (including according to biochemical blood test data: electrolyte content, blood urea nitrogen, bilirubin, liver enzyme activity), as well as complete blood count parameters should be periodically monitored.

Specific problems associated with changes in the international normalized ratio (INR) are possible. Numerous cases of increased activity of vitamin K antagonists have been reported in patients receiving antibiotics. Risk factors include severe infection or inflammation, age, and poor general health. Under these conditions, it is difficult to determine whether the change in INR is a consequence of the infectious disease or its treatment. Nevertheless, certain classes of antibiotics are more frequently mentioned in this regard, namely fluoroquinolones, macrolides, cyclines, co-trimoxazole and some cephalosporins.

Fosfomycin, when used in combinations with penicillins, cephalosporins, carbapenems, aminoglycosides, glycopeptides and fluoroquinolones, exhibits a pronounced synergistic effect; this property of fosfomycin is used in the therapy of severe infections, as well as infections caused by multidrug-resistant pathogens (methicillin-resistant staphylococci, enterococci, enterobacteria, etc.).

Drug Interactions

With concurrent use, metoclopramide reduces the concentration of fosfomycin in blood serum and urine.

Simultaneous use of antacids or calcium salts leads to a decrease in the concentration of fosfomycin in blood plasma and urine.

Fosfomycin, when used in combinations with penicillins, cephalosporins, carbapenems, aminoglycosides, glycopeptides and fluoroquinolones, exhibits a pronounced synergistic effect.

Due to physicochemical incompatibility, Fosfomycin should not be mixed in the same syringe with ampicillin, gentamicin, streptomycin, kanamycin and rifampicin.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.