Fosfomycin Tromethamine

INDICATIONS AND USAGE Fosfomycin tromethamine granules for oral solution is indicated only for the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis . Fosfomycin tromethamine granules for oral solution is not indicated for the treatment of pyelonephritis or perinephric abscess. If persistence or reappearance of bacteriuria occurs after treatment with fosfomycin tromethamine granules for oral solution, other therapeutic agents should be selected. (See PRECAUTIONS and CLINICAL STUDIES sections.)

DOSAGE AND ADMINISTRATION The recommended dosage for women 18 years of age and older for uncomplicated urinary tract infection (acute cystitis) is one sachet of fosfomycin tromethamine granules for oral solution. Fosfomycin tromethamine granules for oral solution may be taken with or without food. Fosfomycin tromethamine granules for oral solution should not be taken in its dry form. Always mix fosfomycin tromethamine granules for oral solution with water before ingesting. (See PREPARATION section.) PREPARATION Fosfomycin tromethamine granules for oral solution should be taken orally. Pour the entire contents of a single-dose sachet of fosfomycin tromethamine granules for oral solution into 3 to 4 ounces of water (1/2 cup) and stir to dissolve. Do not use hot water. Fosfomycin tromethamine granules for oral solution should be taken immediately after dissolving in water.

CONTRAINDICATIONS Fosfomycin tromethamine granules for oral solution is contraindicated in patients with known hypersensitivity to the drug.

ADVERSE REACTIONS Clinical Trials: In clinical studies, drug related adverse events which were reported in greater than 1% of the fosfomycin-treated study population are listed below: Drug-Related Adverse Events (%) in Fosfomycin and Comparator Populations Adverse Events Fosfomycin N=1233 Nitrofurantoin N=374 Trimethoprim/ sulfamethoxazole N=428 Ciprofoxacin N=455 Diarrhea 9.0 6.4 2.3 3.1 Vaginitis 5.5 5.3 4.7 6.3 Nausea 4.1 7.2 8.6 3.4 Headache 3.9 5.9 5.4 3.4 Dizziness 1.3 1.9 2.3 2.2 Asthenia 1.1 0.3 0.5 0.0 Dyspepsia 1.1 2.1 0.7 1.1 In clinical trials, the most frequently reported adverse events occurring in > 1% of the study population regardless of drug relationship were: diarrhea 10.4%, headache 10.3%, vaginitis 7.6%, nausea 5.2%, rhinitis 4.5%, back pain 3.0%, dysmenorrheal 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%. The following adverse events occurred in clinical trials at a rate of less than 1%, regardless of drug relationship: abnormal stools, anorexia, constipation, dry mouth, dysuria, ear disorder, fever, flatulence, flu syndrome, hematuria, infection, insomnia, lymphadenopathy, menstrual disorder, migraine, myalgia, nervousness, paresthesia, pruritus, SGPT increased, skin disorder, somnolence, and vomiting. One patient developed unilateral optic neuritis, an event considered possibly related to fosfomycin tromethamine therapy. Post-marketing Experience: Serious adverse events from the marketing experience with fosfomycin tromethamine outside of the United States have been rarely reported and include: angioedema, aplastic anemia, asthma (exacerbation), cholestatic jaundice, hepatic necrosis, and toxic megacolon. Although causality has not been established, during post marketing surveillance, the following events have occurred in patients prescribed fosfomycin tromethamine: anaphylaxis and hearing loss. Laboratory Changes: Significant laboratory changes reported in U.S. clinical trials of fosfomycin tromethamine without regard to drug relationship include: increased eosinophil count, increased or decreased WBC count, increased bilirubin, increased SGPT, increased SGOT, increased alkaline phosphatase, decreased hematocrit, decreased hemoglobin, increased and decreased platelet count. The changes were generally transient and were not clinically significant. To report SUSPECTED ADVERSE REACTIONS, contact Aucta Pharmaceuticals, Inc at 1- 800- 655- 9902 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions Metoclopramide: When coadministered with fosfomycin tromethamine granules for oral solution, metoclopramide, a drug which increases gastrointestinal motility, lowers the serum concentration and urinary excretion of fosfomycin. Other drugs that increase gastrointestinal motility may produce similar effects. Cimetidine: Cimetidine does not affect the pharmacokinetics of fosfomycin when coadministered with fosfomycin tromethamine granules for oral solution.

DESCRIPTION Fosfomycin tromethamine granules for oral solution contains fosfomycin tromethamine USP, a synthetic, broad spectrum, bactericidal antibiotic for oral administration. It is available as a single-dose sachet which contains white to off-white orange flavored granules consisting of 5.631 grams of fosfomycin tromethamine USP (equivalent to 3 grams of fosfomycin), and the following inactive ingredients: colloidal silicon dioxide, orange flavor (contains dl-alpha-tocopherol, maltodextrin and natural & artificial flavors), saccharin sodium, sucrose and tetrarome mandarin (contains maize maltodextrin, natural flavorings and triacetin). The contents of the sachet must be dissolved in water. Fosfomycin tromethamine USP, a phosphonic acid derivative, is available as (1 R ,2 S )-(1,2-epoxypropyl)phosphonic acid, compound with 2- amino-2-(hydroxymethyl)-1,3-propanediol (1:1). It is a white or almost white powder with a molecular weight of 259.2. Its molecular formula is C 3 H 7 O 4 P.C 4 H 11 NO 3 , and its chemical structure is as follows: str

OVERDOSAGE In acute toxicology studies, oral administration of high doses of fosfomycin tromethamine granules for oral solution up to 5 g/kg were well-tolerated in mice and rats, produced transient and minor incidences of watery stools in rabbits, and produced diarrhea with anorexia in dogs occurring 2 to 3 days after single dose administration. These doses represent 50 to 125 times the human therapeutic dose. The following events have been observed in patients who have taken fosfomycin tromethamine granules for oral solution in overdose: vestibular loss, impaired hearing, metallic taste, and general decline in taste perception. In the event of overdosage, treatment should be symptomatic and supportive.

HOW SUPPLIED Fosfomycin Granules for Oral Solution is a white, orange-flavored granular powder for oral administration. Each single-dose sachet contains granules equivalent to 3 grams of fosfomycin. The product is available as follows: NDC 81033-024-03: 3 g single-dose sachet NDC 81033-024-11: Carton containing 1 single-dose 3 g sachet Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Keep this and all drugs out of the reach of children. For Institutional Use Only