Fosfomycin

Fosfomycin is an antibiotic that fights bacterial infections in the urinary tract. It is available in two formulations:

• Granules for oral solution (Monurol, generic): Used for uncomplicated bladder infections in women
• Intravenous infusion (Contepo): Used for complicated urinary tract infections in adults 18 years and older.

Both forms work against common bacteria that cause urinary tract infections, including Escherichia coli (E. coli).

Fosfomycin has a unique mechanism of action that differs from most other antibiotics, which may make it effective against multidrug-resistant (MDR) bacterial strains.

Mechanism of Action

Fosfomycin works by disrupting bacterial cell wall construction:

• It enters bacteria through two specialized transport channels (glycerol-3-phosphate and hexose-6-phosphate systems)
• Once inside, it permanently attaches to and blocks an enzyme called MurA (phosphoenolpyruvate transferase)
• This enzyme is essential for building peptidoglycan, the structural material that forms bacterial cell walls
• Without functional peptidoglycan synthesis, bacteria cannot maintain their cell walls and die

This bactericidal (bacteria-killing) effect is particularly effective against Enterobacterales, the family of bacteria that includes E. coli and Klebsiella pneumoniae.

Because fosfomycin's mechanism differs from other antibiotic classes, it may work against bacteria that have developed resistance to conventional antibiotics.

Oral Fosfomycin (Monurol, generic)

Used to treat uncomplicated urinary tract infections (acute cystitis) in women caused by:

• Escherichia coli (E. coli)
• Enterococcus faecalis

Not approved for:

• Pyelonephritis (kidney infection)
• Perinephric abscess

Injectable Fosfomycin (Contepo)

Used to treat complicated urinary tract infections (cUTI) in adults 18 years and older, including:

• Acute pyelonephritis (kidney infection)
• cUTIs caused by susceptible E. coli
• cUTIs caused by susceptible Klebsiella pneumoniae.

Electrolyte Abnormalities (Contepo)

Each vial of Contepo contains 1,980 mg of sodium. This high sodium content may cause:

• Increased sodium levels (hypernatremia)
• Decreased potassium levels (hypokalemia)
• Decreased calcium levels (hypocalcemia)
• Decreased phosphorus levels (hypophosphatemia)

What to do:

• Follow a low-sodium diet during treatment
• Your healthcare provider will monitor electrolyte levels and fluid status
• Watch for signs of edema (swelling), especially if you have heart failure, kidney problems, liver cirrhosis, high blood pressure, or lung problems

QT Prolongation (Contepo)

Contepo may prolong the QT interval on electrocardiograms, which can lead to dangerous heart rhythm problems.

Avoid Contepo if you have:

• Known QT prolongation
• Ventricular arrhythmias
• History of torsade de pointes

Liver Enzyme Elevations (Contepo)

Increases in liver enzymes (ALT and AST) have been reported. Regular monitoring of liver function is recommended during treatment.

Hypersensitivity Reactions

Allergic reactions, including rash, hives (urticaria), and anaphylaxis, may occur with both formulations. Inform your healthcare provider about any previous reactions to fosfomycin before starting treatment.

Neutropenia (Contepo)

Low white blood cell counts, including severe cases (agranulocytosis), have occurred with intravenous fosfomycin. Complete blood counts should be monitored during therapy. If this occurs, Contepo will be discontinued.

Clostridioides difficile Infection

Like most antibiotics, fosfomycin may cause severe diarrhea due to C. difficile bacteria. This has been reported with nearly all systemic antibacterial agents.

Contact your healthcare provider if:

• Diarrhea develops during or after treatment
• Diarrhea is watery or bloody

Get emergency medical help if you have signs of an allergic reaction:

• Hives
• Difficult breathing
• Swelling of your face, lips, tongue, or throat

Call your doctor at once if you have:

• Diarrhea that is watery or bloody
• New or worsening bladder symptoms (burning, painful urination)
• Signs of electrolyte problems (for Contepo): confusion, irregular heartbeat, muscle weakness, tingling sensations
• Signs of low white blood cell count: fever, chills, mouth sores, skin sores

This is not a complete list of side effects. Call your doctor for medical advice about side effects.

To report side effects:

• Oral fosfomycin: FDA at 1-800-FDA-1088
• Contepo: Meitheal Pharmaceuticals at 1-844-824-8426 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Tell Your Doctor If You Have:

Allergies:

• Any previous allergic reactions to fosfomycin (oral or intravenous)
• Allergies to any ingredients in the medication

Heart conditions (especially for Contepo):

• Heart rhythm problems or QT prolongation
• Ventricular arrhythmias
• History of torsade de pointes
• Cardiac insufficiency or congestive heart failure

Kidney problems:

• Renal impairment or reduced kidney function
• If you are receiving hemodialysis treatments

Liver disease:

• Cirrhosis or other liver conditions

Other medical conditions (especially for Contepo):

• High blood pressure (hypertension)
• History of fluid retention or edema
• Pulmonary edema or fluid in the lungs
• Electrolyte imbalances (low potassium, low calcium, low phosphorus, or high sodium)
• Hyperaldosteronism or other hormone disorders
• History of low white blood cell counts or neutropenia

Also, Tell Your Doctor If You Are:

• Pregnant or planning to become pregnant: It is not known if fosfomycin affects an unborn baby
• Breastfeeding or planning to breastfeed: Oral fosfomycin: Discuss with your doctor Contepo: Not recommended during treatment and for 24 hours after the last dose
• Taking other medications, especially: Metoclopramide (for oral fosfomycin) Medications that prolong the QT interval (for Contepo)
• On a sodium-restricted diet (for Contepo)

Important Restrictions:

• Oral fosfomycin should not be given to children younger than 12 years old
• Contepo is only approved for adults 18 years and older
• You should not use fosfomycin if you are allergic to it.

Common Side Effects (Oral Fosfomycin)

• Nausea, upset stomach, stomach pain
• Diarrhea
• Headache, dizziness
• Weakness
• Rash
• Sore throat, runny nose
• Back pain
• Menstrual pain, vaginal itching, or discharge.

Common Side Effects (Contepo)

• Elevated liver enzymes (transaminases)
• Low potassium (hypokalemia)
• Low white blood cell count (neutropenia)
• Nausea
• Vomiting
• Diarrhea
• Low calcium (hypocalcemia)
• High sodium (hypernatremia)
• Headache
• Low phosphorus (hypophosphatemia).

Oral Fosfomycin (Monurol) Dosage

Adults and children 12 years and older:

• Dose: 3 grams (1 sachet) taken once as a single dose
• How to take: Mix powder with 3-4 ounces (½ cup) of cold water, stir, and drink immediately

Important instructions:

• Do not take the dry powder without mixing with water
• Do not mix with hot water
• May take with or without food
• To ensure you get the full dose, add a little more water to the glass after drinking, swirl gently, and drink
• Fosfomycin is usually given in only one dose; do not take more unless your doctor tells you to
• It may take 2-3 days before symptoms improve
• Call your doctor if symptoms do not improve within 3 days

Injectable Fosfomycin (Contepo) Dosage

Contepo is administered by a healthcare provider in a hospital or clinic setting.

Standard dosing (for patients with creatinine clearance greater than 50 mL/min):

• Dose: 6 grams every 8 hours
• Administration: Intravenous infusion over 1 hour
• Duration: Up to 14 days

Renal Impairment Dosing

For patients with reduced kidney function (creatinine clearance 50 mL/min or less):

Hemodialysis patients: Contepo should be administered after dialysis sessions, as 60-80% of the medication is removed during hemodialysis.

• Oral fosfomycin: Given as a single dose and does not have a daily dosing schedule
• Contepo: Administered by healthcare providers who will maintain the proper schedule

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include hearing problems and an altered sense of taste.

Oral Fosfomycin Interactions

Metoclopramide: May reduce fosfomycin effectiveness. Tell your doctor if you are taking metoclopramide.

Contepo Interactions

Medications that prolong the QT interval: Avoid co-administration with Contepo as this may increase the risk of dangerous heart rhythm problems.

General Advice

Tell your doctor about all your medications, including:

• Prescription medications
• Over-the-counter medicines
• Vitamins
• Herbal products

Not all possible drug interactions are listed here.

Oral Fosfomycin

• Store at room temperature away from moisture and heat
• Keep the powder in its original package until you are ready to mix your dose

Contepo

• Administered in healthcare settings
• Healthcare providers will handle storage and preparation.

Oral Fosfomycin (Monurol)

• Active ingredient: 3 grams fosfomycin tromethamine per sachet
• Inactive ingredients: tangerine, orange, saccharin, sucrose.

Injectable Fosfomycin (Contepo)

• Active ingredient: 6 grams of fosfomycin (equivalent to 7.9 grams fosfomycin disodium) per vial
• Inactive ingredient: Succinic acid (150 mg) for pH adjustment
• Each gram of fosfomycin disodium contains 330 mg of sodium (total of 1,980 mg sodium per vial).