Fosfomycin (Monurol)

1. Health Canada Product Monograph — Fosfomycin

• Fosfomycin is used to treat acute uncomplicated lower urinary tract infections (acute cystitis) in women 18 years of age and older caused by susceptible bacteria such as Escherichia coli and Enterococcus faecalis.
• Fosfomycin is not indicated for kidney infections (pyelonephritis) or infections around the kidney (perinephric abscess).
• Fosfomycin should only be used when a bacterial infection is proven or strongly suspected, to help reduce the development of antibiotic-resistant bacteria.

• Fosfomycin crosses the placenta, and its safety for treating infections during pregnancy has not been established.
• Fosfomycin should not be used during pregnancy unless clearly needed, after weighing the potential benefit to the mother against the potential risk to the fetus.

• Fosfomycin may pass into human breast milk.
• A decision should be made whether to stop breastfeeding or avoid fosfomycin, weighing the benefit to the mother against the potential risk to the nursing infant.

• Clinical studies show no meaningful differences in the safety or effectiveness of fosfomycin in older adults compared with younger women.
• No dose adjustment is needed in older adults, since fosfomycin's pharmacokinetics are not significantly altered by age alone.

• Fosfomycin has not been studied in patients under 18 years of age, and Health Canada has not approved its use in this age group.

• Fosfomycin is given as a single dose: one 3 g sachet, dissolved in about 125 mL (half a cup) of cold water and taken immediately after dissolving.
• Only a single dose should be used to treat one episode of acute cystitis; repeated daily dosing does not improve cure rates and increases the risk of side effects.
• No dose adjustment is needed for mild-to-moderate liver impairment or for older adults.
• Before use in patients with severe kidney impairment (creatinine clearance below 30 mL/min) or those on hemodialysis, the prescriber should weigh the potential benefits against the potential risks, since fosfomycin is mainly cleared by the kidneys.
• Fosfomycin should generally not be taken at the same time as other medications, if this can be avoided.
• Because treatment is a single dose, there is no scheduled second dose to miss; if the original dose was missed, it should be taken on an empty stomach or at least 2-3 hours after the next meal.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• Experience with oral fosfomycin overdose is limited.
• Reported effects of fosfomycin overdose from intravenous use include low muscle tone, drowsiness, electrolyte disturbances, low platelet count, and impaired blood clotting.
• Management of overdose is symptomatic and supportive, with monitoring of blood electrolyte levels.
• Adequate fluid intake should be encouraged to promote urinary elimination of the drug.
• Fosfomycin can be effectively removed from the body by hemodialysis if needed.

• Diarrhea may occur and is usually mild and self-limiting.
• Vaginitis (vaginal irritation or infection) may occur.
• Nausea may occur.
• Headache may occur.
• Dizziness may occur.
• Weakness (asthenia) may occur.
• Upset stomach (dyspepsia) may occur.
• Back pain may occur.
• Runny nose (rhinitis) may occur.
• Skin rash may occur.
• Abdominal pain may occur.
• Sore throat (pharyngitis) may occur.
• Menstrual cramps (dysmenorrhea) may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Serious allergic reactions, including anaphylaxis and anaphylactic shock, have been reported and can be life-threatening.
• Fosfomycin contains sulphites, which can rarely cause severe allergic reactions and bronchospasm, particularly in sulphite-sensitive individuals.
• Clostridium difficile-associated diarrhea and colitis can occur, ranging from mild diarrhea to severe, potentially fatal bowel inflammation, and can develop even weeks after treatment.
• A single case of optic neuritis (inflammation of the optic nerve) has been reported as possibly related to fosfomycin.
• Rare cases of angioedema, aplastic anemia, hepatic necrosis, and cholestatic jaundice have been reported after fosfomycin use.
• Impaired hearing and vestibular disturbances affecting balance have been reported rarely.
• Exacerbation of asthma has been reported rarely.
• Seek immediate medical attention for swelling of the lips, throat, or tongue, difficulty breathing, or severe or bloody diarrhea with fever.

• Use with caution in patients with severe kidney impairment or those undergoing hemodialysis, since fosfomycin is cleared by the kidneys and its safety has not been well studied in this group.
• Use with caution in patients with a hereditary intolerance to fructose, glucose-galactose malabsorption, or sucrase-isomaltase insufficiency, since the product contains sucrose.
• Use with caution in patients with a sulphite sensitivity, since the flavourings contain sulphites.
• Use with caution when driving or operating machinery, since dizziness has been reported.
• If symptoms of a urinary tract infection persist after treatment, the diagnosis should be re-evaluated, since this may indicate a complicated infection or resistant bacteria.
• Fosfomycin is chemically unrelated to penicillins and other common allergy-causing antibiotics, but patients with a history of drug allergies should still discuss this with their healthcare professional before use.

• Contraindicated in patients with known hypersensitivity to fosfomycin or to any ingredient in the formulation, including the mandarin and orange flavourings, which contain sulphites.

• Metoclopramide, which increases gastrointestinal motility, can lower fosfomycin blood and urine concentrations; other drugs that speed up gut motility may have a similar effect.
• Probenecid should not be combined with fosfomycin, since it significantly reduces fosfomycin's kidney clearance and urinary concentration, potentially reducing effectiveness.
• Cimetidine does not affect fosfomycin's levels or urinary concentration and can be used together without dose adjustment.
• Fosfomycin should generally not be taken together with other medications, if this can be avoided, to reduce the risk of unknown interactions.
• Calcium-containing products, including antacids, do not need to be avoided with fosfomycin, since no meaningful interaction with calcium has been found.

• Fosfomycin should be taken on an empty stomach, at least 2 to 3 hours after a meal, since food delays and reduces its absorption and urinary concentration.

• Fosfomycin is taken as a single dose, on an empty stomach or at least 2 to 3 hours after eating, dissolved in cold water and taken right away.

• Store fosfomycin powder at controlled room temperature between 15°C and 30°C.

• Fosfomycin (Monurol) is a one-time, single-dose antibiotic used to treat a bladder infection in adult women.
• Take the entire dose on an empty stomach, or at least 2-3 hours after eating, mixed in cold water and taken right away.
• Your symptoms should improve within 2 to 3 days; contact your healthcare professional if they have not improved by day 4 or if the infection returns.
• Seek immediate medical attention for signs of a serious allergic reaction or severe, persistent diarrhea.
• Complete this one-time antibiotic course exactly as directed, and never share it with anyone else.