Fosfomycin

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications: 

• Acute uncomplicated lower urinary tract infections caused by sensitive E. coli, in women and female adolescents
• Prophylaxis in diagnostic and surgical transurethral procedures in men

Contraindications

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Severe renal insufficiency (creatinine clearance <10ml/min)
• Patients undergoing haemodialysis

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment (CrCl>10ml/min)
• Renal impairment (CrCl<10ml/min) (Recommendations in other jurisdictions)
• Hepatic impairment
• Elderly (>75 years) (South African recommendations)
• Elderly (Recommendations in other jurisdictions)
• Persistent infections
• Male patients
• Fructose intolerance
• Glucose-galactose malabsorption
• Sucrase-isomaltase insufficiency
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: gra, pow

Dosages below include:

• South African Standard Treatment Guideline indications and dosages
• South African registered indications and dosages

Infections caused by: Escherichia coli

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African Standard Treatment Guideline indications and dosages

Cystitis in pregnancy
Uncomplicated cystitis 
- If gentamicin is unavailable/contraindicated
Uncomplicated community acquired cystitis

• Oral (gra, pow): 3g, as a single dose
  (STG, Adult 2019; Adult 2023; PHC 2020)

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South African registered indications and dosages

Acute uncomplicated lower urinary tract infections caused by sensitive E. coli, in women

• Oral (gra, pow): 3g, as a single dose

Prophylaxis prior to transurethral surgery and diagnostic procedures in men

• Oral (gra, pow): First dose: 3g, 3hrs before surgery; Second dose: 3g, 24hrs after surgery

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Granules: To be reconstituted in water and taken at least two hours before meals
Powder: The contents of a sachet should be dissolved in a glass of water and taken immediately
after its preparation. Should be taken on an empty stomach, either 1 hour before or at least 2 hours after meals and preferably before bedtime after emptying the bladder

Paed. forms avail. in SA and covered in this monograph: gra, pow

Infections caused by: Escherichia coli

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

South African registered indications and dosages

Acute uncomplicated lower urinary tract infections caused by sensitive E. coli, in female adolescents

Younger than 12 years

• Not established for use

Older than 12 years

• See adult dosage

Pregnancy

• Caution
• Only limited data on the safety of fosfomycin treatment during 1st trimester of pregnancy (n=152) are available. These data do not raise any safety signal for teratogenicity so far. Fosfomycin crosses the placenta
• Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity
• Fosfomycin should only be used during pregnancy, if clearly necessary

Breastfeeding

• Caution
• Fosfomycin is excreted in human milk in low quantities. If clearly necessary, a single dose of oral fosfomycin can be used during breastfeeding

Fertility

• No data in humans are available. In male and female rats, oral administration of fosfomycin up to 1000mg/kg/day did not impair fertility

Renal Impairment

South African recommendations

• CrCl>10ml/min: Caution; no dose adjustment recommended
  Urinary concentrations of fosfomycin remain effective for 48 hours after a usual dose if creatinine clearance is above 10ml/min
  In patients with moderately reduced renal function (creatinine clearance >80ml/min), the half-life of fosfomycin is prolonged but urinary concentration remains therapeutically adequate
  Fosfomycin is principally excreted by the kidney. Caution should be exercised in administering this antibiotic to patients with impaired renal function
• CrCl<10ml/min: Contraindicated

Recommendations in other jurisdictions

• CrCl>10ml/min: Caution; no dose adjustment recommended 
  In patients with impaired renal function, the elimination half-life is increased proportionally to the degree of renal insufficiency. Urinary concentrations of fosfomycin in patients with impaired renal function remain effective for 48 hours after a usual dose if creatinine clearance is above 10 ml/min
• CrCl<10ml/min: Caution; not recommended 
  Use in patients with CrCl<10ml/min is not recommended

Hepatic Impairment

• Caution; no information available

Elderly

South African recommendations

• ≤75 years: No dose adjustment recommended
• >75 years: Caution; no dose adjustment recommended
  In older people, fosfomycin clearance is reduced in line with the physiological reduction in renal function, the half-life of fosfomycin is prolonged but urinary concentration remains therapeutically adequate

Recommendations in other jurisdictions

• Caution; no dose adjustment recommended
  In older people fosfomycin clearance is reduced in line with the age-related reduction in renal function

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness

Gastrointestinal Disorders

• Dyspepsia
• Diarrhoea
• Nausea and vomiting
• Abdominal pain
• Antibiotic-associated colitis

Genitourinary Disorders

• Vulvovaginitis

Skin and Subcutaneous Tissue Disorders

• Rash
• Urticaria
• Pruritus
• Angioedema

Immune, Blood and Lymphatic System Disorders

• Anaphylactic reactions
  - Anaphylactic shock
  - Hypersensitivity

• Metoclopramide
• Agents that increase gastrointestinal motility
• Oral anticoagulants (See additional prescribing points)

Other interactions

• Food

None routine

Alteration in INR

• Numerous cases of increased antivitamin K antagonists activity have been reported in patients receiving antibiotics
• Risk factors include severe infection or inflammation, age and poor general health
• Under these circumstances, it is difficult to determinate whether the alteration in INR is due to the infectious disease or its treatment
• However, certain classes of antibiotics are more often involved and in particular: fluoroquinolones, macrolides, cyclins, cotrimoxazole and certain cephalosporins

Antibiotic-associated diarrhoea

• Antibiotic-associated diarrhoea (AAD) has been reported with use of nearly all antibacterial medicines, including fosfomycin AAD may range in severity from mild diarrhoea to fatal colitis
• Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with fosfomycin (including several weeks after treatment), may be symptomatic of Clostridium difficile-associated disease (CDAD)
• It is therefore important to consider this diagnosis in patients who develop serious diarrhoea during or after treatment with fosfomycin
• If CDAD is suspected or confirmed, appropriate treatment should be initiated without delay
• Anti-peristaltic medicines are contraindicated in this clinical situation

Fosfomycin exerts a bactericidal effect on proliferating pathogens by preventing the enzymatic synthesis of the bacterial cell wall. Fosfomycin inhibits the first stage of intracellular bacterial cell wall synthesis by blocking peptidoglycan synthesis. Fosfomycin is actively transported into the bacterial cell via two different transport systems (the sn-glycerol-3-phosphate and hexose-6 transport systems).

Spectrum of activity: Escherichia coli 

Granules (per sachet) 3g

• Actizone (Actor Pharma)
• Fomnos (Sandoz SA)
• Urizone (Adcock Ingram) originator

Powder (per sachet) 3g

• Tractinfect (Pharmacare Limited)