Fosfomycin Sodium for Injection BP 4g

  1. Name of the medicinal product

Fosfomycin Sodium 40mg/ml powder for solution for infusion BP Taj Pharma

  1. Qualitative and quantitative composition

One ml of reconstituted solution contains 40mg fosfomycin.

Each bottle with 5.38 g of powder contains 5.28g disodium fosfomycin, corresponding to 4g fosfomycin and 1.28g sodium, for reconstitution in 100 ml of solvent.

For a full list of excipients, see section 6.1.

  1. Pharmaceutical form

Powder for solution for infusion.

  1. Clinical particulars

4.1 Therapeutic indications

Fosfomycin is indicated for the treatment of the following infections in adults and children including neonates (see section 5.1):

– Osteomyelitis

– Complicated urinary tract infections

– Nosocomial lower respiratory tract infections

– Bacterial meningitis

– Bacteraemia that occurs in association with, or is suspected to be associated with, any of the infections listed above

Fosfomycin should be used only when it is considered inappropriate to use antibacterial agents that are commonly recommended for the initial treatment of the infections listed above, or when these alternative antibacterial agents have failed to demonstrate efficacy.

For information regarding the combination with other antibiotics see section 4.4 and 4.5.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration

The daily dose of fosfomycin is determined based on the indication, severity and site of the infection, susceptibility of the pathogen(s) to fosfomycin and the renal function. In children, it is also determined by age and body weight.

Adults and adolescents ≥ 12 years of age (> 40 kg):

Fosfomycin is primarily excreted renally unchanged. The general dosage guidelines for adults with estimated creatinine clearance > 80 ml/min are as follows:

IndicationDaily dose
Osteomyelitis12–24 g a in 2–3 divided doses
Complicated urinary tract infection12–16 g in 2–3 divided doses
Nosocomial lower respiratory tract infection12–24 g a in 2–3 divided doses
Bacterial meningitis16–24 g a in 3–4 divided doses

Individual doses must not exceed 8 g.

a The high-dose regimen in 3 divided doses should be used in severe infections expected or known to be caused by less susceptible bacteria.

There are limited safety data in particular for doses in excess of 16 g/day. Special caution is advised when such doses are prescribed.

Dosage in renal insufficiency

The dose recommendations for patients with renal impairment are based on pharmacokinetic modelling and limited clinical data; safety and efficacy have not yet been evaluated in clinical trials.

It is unclear if dose reductions are necessary for patients with an estimated creatinine clearance between 40–80 ml/min. Great caution should be exercised in these cases, particularly if doses at the higher end of the recommended range are considered.

In patients with impaired renal function the dose of fosfomycin must be adjusted to the degree of renal impairment.

Dose titration should be based on creatinine clearance values. In adults, creatinine clearance may be calculated according to the following formula by Cockroft and Gault:

In order to calculate CLCR in women, the result of this formula is multiplied by 0.85.

Dosage table for patients with impaired renal function:

CLCR patientCLCR patient/ CLCR normalDaily dosage recommended a
40 ml/min0.33370% (in 2–3 divided doses)
30 ml/min0.25060% (in 2–3 divided doses)
20 ml/min0.16740% (in 2–3 divided doses)
10 ml/min0.08320% (in 1–2 divided doses)

a The dose is expressed as a proportion of the dose that would have been considered appropriate if the patient’s renal function were normal

The first dose should be increased by 100% (loading dose), but must not exceed 8 g.

Patients undergoing renal replacement therapy

Patients undergoing chronic intermittent dialysis (every 48 hours) should receive 2 g of fosfomycin at the end of each dialysis session.

During continuous veno-venous hemofiltration (post-dilution CVVHF), fosfomycin is effectively eliminated. Patients undergoing post-dilution CVVHF will not require any dose adjustment (see section 5.2).

No clinical data exist for intravenous fosfomycin in patients undergoing pre-dilution CVVHF or other forms of renal replacement therapy.

Hepatic impairment

There are no data indicating that dose adjustment is necessary in patients with hepatic impairment.

Elderly patients

The recommended doses for adults should be used in elderly patients. Caution is advised when considering the use of doses at the higher end of the recommended range (see also recommendations on dosage for patients with impaired renal function).

Paediatric population

Dose recommendations are based on very limited data.

Neonates, infants and children < 12 years of age (< 40 kg)

The dosage of fosfomycin in children should be based on age and body weight (BW):

Age/weightDaily dose
Premature neonates

(age a < 40 weeks)

100mg/kg BW in 2 divided doses
Neonates

(age a 40–44 weeks)

200mg/kg BW in 3 divided doses
Infants 1–12 months

(up to 10 kg BW)

200–300 bmg/kg BW in 3 divided doses
Infants and children aged 1–12 years

(10–40 kg BW)

200–400 bmg/kg BW in 3–4 divided doses

a Sum of gestational and postnatal age.

b The high-dose regimen may be considered for severe infections and or serious infections (such as meningitis), in particular when known or suspected to be caused by organisms with moderate susceptibility.

No dose recommendations can be made for children with renal impairment.

Method and duration of administration

Method of administration

Disodium fosfomycin is intended for intravenous administration. The duration of infusion should be at least 15 minutes for the 2 g pack size, at least 30 minutes for the 4 g pack size and at least 60 minutes for the 8 g pack size.

Use only clear solutions.

As damaging effects can result from inadvertent intra-arterial administration of products not specifically recommended for intra-arterial therapy, it is essential to ensure that fosfomycin is only administered into veins.

For preparation of the solution for infusion see section 6.6.

Duration of treatment

Treatment duration should take into account the type of infection, the severity of the infection as well as the patient’s clinical response. Relevant therapeutic guidelines should be adhered to when deciding treatment duration.

4.3 Contraindications

– Hypersensitivity to the active substance, fosfomycin, or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Consideration should be given to co-administering intravenous fosfomycin with another antibacterial agent, taking into account the remaining susceptibilities of the pathogen(s) under treatment. As it is unknown whether the development of resistance to intravenous fosfomycin is higher when it is used as a monotherapy, co-administration with other antibacterials should also be considered in order to prevent the emergence of resistance.

1 g fosfomycin (equivalent to 1.32 g disodium fosfomycin) contains 14 mmol (320mg) sodium. One bottle with 2 g of fosfomycin contains 28 mmol (640mg) sodium, one bottle with 4 g fosfomycin contains 56 mmol (1280mg) sodium and one bottle with 8 g of fosfomycin contains 111 mmol (2560mg) sodium.

A high sodium load associated with the use of fosfomycin may result in decreased levels of potassium in serum or plasma. A low-sodium diet is recommended during treatment. The substitution of potassium may be necessary in some cases. Serum electrolyte levels and water balance must be monitored during therapy. Caution is advised when fosfomycin is used in patients with cardiac insufficiency, hypertension, hyperaldosteronism, hypernatraemia or pulmonary oedema.

Acute, potentially life-threatening hypersensitivity reactions (anaphylactic shock) may occur in very rare cases. At the first signs (including sweating, nausea, cyanosis), the infusion of fosfomycin must be immediately discontinued. The intravenous line should be left in place. Depending upon the clinical situation, appropriate emergency measures may need to be initiated.

Antibacterial agent-associated colitis and pseudo-membranous colitis have been reported with nearly all antibacterial agents including fosfomycin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of fosfomycin. Discontinuation of therapy with fosfomycin and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given.

In patients with severe renal insufficiency (creatinine clearance ≤ 40ml/min), the elimination of fosfomycin is substantially slowed. See section 4.2 for appropriate dosing of fosfomycin in renal insufficiency.

4.5 Interaction with other medicinal products and other forms of interaction

No drug-drug interaction studies have been performed with fosfomycin. To date, no clinically relevant pharmacological interactions between fosfomycin and other agents (drugs, stimulants or foodstuffs) have been reported.

Combination with other antibiotics

In-vitro tests have shown that the combination of fosfomycin with a β-lactam antibiotic such as penicillin, ampicillin, cefazolin or the class of carbapenems, usually shows an additive to synergistic effect. The same applies to the combination of fosfomycin with most anti-staphylococcal (linezolid, quinupristin/dalfopristin, moxifloxacin) agents in the treatment of staphylococcal infections. The combination of fosfomycin with aminoglycosides has predominantly indifferent to additive effects.

4.6 Fertility, pregnancy and lactation

Fertility

To date, in humans no reduction in fertility after therapy with fosfomycin has been reported. In male and female rats, reduced fertility was observed after the oral administration of fosfomycin at supra-therapeutic doses (see section 5.3.).

Pregnancy

For fosfomycin, no clinical data on pregnancies are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). Fosfomycin should therefore not be prescribed to pregnant women unless the benefit outweighs the risk.

Lactation

After the administration of fosfomycin, low quantities of fosfomycin were found in human milk. Fosfomycin should therefore not be administered during lactation, unless the benefit outweighs the risk.

4.7 Effects on ability to drive and use machines

Occasionally, even if the product is correctly administered, side effects may occur which impair the ability to drive and use machines (see also section 4.8).

4.8 Undesirable effects

Summary of the safety profile

The most commonly reported adverse reactions during treatment are gastrointestinal disturbances and injection site reactions. Other important adverse reactions include hypokalaemia and/or hypernatraemia.

Tabulated list of adverse reactions

Undesirable effects are listed by body system and frequency in accordance with the following classification:

Very common:≥ 1/10
Common:≥ 1/100 to < 1/10
Uncommon:≥ 1/1,000 to < 1/100
Rare:≥ 1/10,000 to < 1/1,000
Very rare:< 1/10,000
Not known:cannot be estimated from the available data
System Organ ClassFrequency CategoryAdverse Drug Reactions
Blood and lymphatic system disordersRareAplastic anaemia, eosinophilia
Frequency not knownAgranulocytosis, granulocytopenia, leucopenia, pancytopenia, thrombocytopenia, neutropenia
Immune system disordersVery rareAnaphylactic shock (see section 4.4)
Metabolism and nutrition disordersUncommonDecreased appetite, hypernatraemia and/or hypokalaemia (see section 4.4), oedema
Psychiatric disordersFrequency not knownConfusion
Nervous system disordersUncommonDysgeusia, headache
Eye disordersVery rareVisual impairment
Ear and labyrinth disordersUncommonVertigo
Cardiac disordersFrequency not knownTachycardia
Respiratory, thoracic and mediastinal disordersUncommonDyspnoea
Frequency not knownAsthmatic attack
Gastrointestinal disordersCommonRetching, stomach ache
UncommonNausea, vomiting, diarrhoea
Frequency not knownPseudomembranous colitis (see section 4.4)
Hepatobiliary disordersUncommonBlood alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase increased (transient)
Very rareFatty liver (completely reversible after discontinuation of fosfomycin)
Frequency not knownHepatitis, cholestatic hepatitis, icterus
Skin and subcutaneous tissue disordersUncommonRash
Frequency not knownAngioedema, facial oedema, pruritus, urticaria
General disorders and administration site conditionsCommonInjection site phlebitis
UncommonFatigue

Description of selected adverse reactions

Hypokalaemia may result in diffuse symptoms such as weakness, tiredness or oedema and/or muscle twitching. Severe forms may cause hyporeflexia and cardiac arrhythmia. Hypernatraemia may be associated with hypertension and signs of fluid overload such as oedema (see section 4.4).

Paediatric population

Limited safety information is available from the paediatric population. Frequency, type and severity of adverse reactions may be expected to be similar to the adult population.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

To date, no cases of accidental overdose with clinically relevant intolerances have been reported. If an overdose is believed to have taken place, the patient must be monitored (particularly for plasma/serum electrolyte levels) and treated symptomatically. Fosfomycin is effectively cleared from the body by haemodialysis with a mean elimination half-life of approximately 4 hours.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: antibiotics for systemic use, other antibacterials

Mode of action

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).

Pharmacokinetic (PK)/pharmacodynamic (PD) relationship

Limited data indicate that fosfomycin most likely acts in a time-dependent manner.

Resistance mechanism

Main mechanism of resistance is a chromosomal mutation causing an alteration of the bacterial fosfomycin transport systems. Further resistance mechanisms, which are plasmid- or transposon-borne, cause enzymatic inactivation of fosfomycin by binding the molecule to glutathione or by cleavage of the carbon-phosphorus-bond in the fosfomycin molecule, respectively.

Cross-resistance

The mode of action of fosfomycin differs from that of all other antibiotic classes. Fosfomycin was generally found to be active in-vitro against clinical isolates of methicillin-resistant staphylococci, vancomycin-resistant enterococci, penicillin- and erythromycin-resistant streptococci and multiresistant Pseudomonas.

Antimicrobial spectrum of fosfomycin (in vitro)

The data predict only the probability of micro-organism susceptibility to fosfomycin.

For intravenous fosfomycin, the susceptibility breakpoints established by the European Committee on Antimicrobial Susceptibility Testing are as follows (EUCAST breakpoint table version 5.0, 2015):

Speciessusceptibleresistant
Enterobacteriaceae≤ 32mg/l> 32mg/l
Staphylococcus spp.≤ 32mg/l> 32mg/l

The prevalence of acquired resistance of individual species may vary geographically and over time. Local information about the resistance situation is therefore necessary, particularly in order to ensure appropriate treatment of severe infections.

In-vitro activity spectrum of fosfomycin and resistance

The following table is based on the breakpoint according to EUCAST and comprises organisms relevant for the approved indications:

Commonly susceptible species
Aerobic Gram-positive microorganisms
Staphylococcus aureus
Streptococcus pyogenes
Streptococcus pneumoniae
Aerobic Gram-negative microorganisms
Citrobacter spp.
Edwardsiella spp.
Enterobacter cancerogenus
Escherichia coli
Haemophilus influenzae
Klebsiella oxytoca
Neisseria spp.
Proteus mirabilis
Proteus penneri
Providencia rettgeri
Anaerobic microorganisms
Peptococcus spp.
Peptostreptococcus spp.
Species in which acquired resistance may be a problem
Gram-positive microorganisms
Enterococcus faecalis
Staphylococcus epidermidis
Gram-negative microorganisms
Enterobacter cloacae
Klebsiella pneumonia
Proteus inconstans
Pseudomonas aeruginosa
Serratia marcescens
Inherently resistant species
Gram-negative microorganisms
Morganella morganii
Anaerobic microorganisms
Bacteroides spp.

The physiologically important apathogenic anaerobic species, Lactobacillus and Bifidobacterium, are not susceptible to fosfomycin.

5.2 Pharmacokinetic properties

Pharmacokinetics

A single intravenous infusion of 4 g and 8 g of fosfomycin in young healthy males resulted in maximum serum concentrations (Cmax) of approx. 200 and 400 μg/ml, respectively. The serum half-life was approx. 2 hours. In elderly and/or critically ill male and female subjects, single intravenous doses of 8 g of fosfomycin resulted in mean Cmax and half-lives in plasma of approximately 350–380 µg/ml and 3.6–3.8 h, respectively.

Distribution

The apparent volume of distribution of fosfomycin is approx. 0.30 l/kg body weight. Fosfomycin is distributed well to tissues. High concentrations are reached in eyes, bones, wound secretions, musculature, cutis, subcutis, lungs and bile. In patients with inflamed meninges, cerebrospinal fluid concentrations reach approx. 20–50% of the corresponding serum levels. Fosfomycin passes the placental barrier. Low quantities were found in human milk (about 8 % of the serum concentrations). The plasma protein binding is negligible.

Metabolism

Fosfomycin is not metabolised by the liver and does not undergo enterohepatic circulation. No accumulation is therefore to be expected in patients with hepatic impairment.

Elimination

80–90% of the quantity of fosfomycin administered to healthy adults is eliminated renally within 10 hours after a single intravenous administration. Fosfomycin is not metabolised, i.e. the biologically active compound is eliminated. In patients with normal or mildly to moderately impaired renal function (creatinine clearance ≥ 40 ml/min), approximately 50–60% of the overall dose is excreted within the first 3-4 hours.

Linearity

Fosfomycin shows linear pharmacokinetic behaviour after intravenous infusion of therapeutically used doses.

Special populations

Very limited data are available in special populations.

Elderly

No dose adjustment is necessary based on age alone. However, renal function should be assessed and the dose should be reduced if there is evidence of renal impairment (see section 4.2).

Paediatric population

The pharmacokinetics of fosfomycin in children and adolescents aged 3–15 years as well as in term newborns with normal renal function are generally similar to those of healthy adult subjects. However, in renally healthy neonates and infants up to 12 months, the glomerular filtration rate is physiologically decreased compared to older children and adults. This is associated with a prolongation of the elimination half-life of fosfomycin in dependence on the stage of renal maturation.

Renal insufficiency

In patients with impaired renal function, the elimination half-life is increased proportionally to the degree of renal insufficiency. Patients with creatinine clearance values of 40 ml/min or less require dose adjustments (see also section 4.2. “Dosage in renal insufficiency” for further details).

In a study investigating 12 patients under CVVHF customary polyethylene sulfone haemofilters with a membrane surface of 1.2 m2 and a mean ultrafiltration rate of 25 ml/min were employed. In this clinical setting, the mean values of plasma clearance and elimination half-life in plasma were 100 ml/min, and 12h, respectively.

Hepatic insufficiency

There is no requirement for dosage adjustments in patients with hepatic insufficiency since the pharmacokinetics of fosfomycin remains unaffected in this patient group.

5.3 Preclinical safety data

Subacute and chronic toxicity

The toxicity of fosfomycin following repeated administration for up to 6 months was evaluated in rats, dogs, rabbits and monkeys. At high intra-peritoneal doses of fosfomycin (> 500mg/kg /day), rats developed respiratory arrest, tetanic cramps, anaemia, a reduction of blood protein levels, increased serum cholesterol and reduced blood glucose. Furthermore, dogs and monkeys experienced diarrhoea due to antibiotic-related changes in the intestinal flora following intravenous administration of doses of higher than 250mg/kg /day and 500mg/kg /day, respectively. In the rabbit, no toxicity was observed following intravenous administration of 400mg/kg /day for a period of 1 month.

Reproductive toxicity

Fertility

In male and female rats, following repeated administration (via a pharyngeal tube) of up to 1400mg/kg /day reduced fertility was observed at the maximum dose tested.

Teratogenicity

Fosfomycin was administered to mice, rats and rabbits via pharyngeal tube at maximum doses of 2 x 120mg/kg /day, 1400mg/kg /day and 420mg/kg /day, respectively or intravenously to mice and rabbits at 55.3mg/kg /day, and up to 250mg/kg /day, respectively. There was no evidence of embryotoxicity or teratogenicity.

Perinatal and postnatal toxicity

In rats, a maximum dose of 2800mg/kg /day was administered via a pharyngeal tube. There was no evidence of foetal or peri- and postnatal toxicity.

Mutagenicity

In-vitro tests were performed to test the alkylating capacity and the mutagenic effect of fosfomycin. Fosfomycin showed no alkylating effect. In the Ames test, no mutagenic effect was seen in test strains of Salmonella typhimurium (TA 98, TA 100, TA 1535, TA 1537 and TA 1538, with and without addition of rat-liver homogenate) after exposure to fosfomycin at up to 1600 µg/ml.

  1. Pharmaceutical particulars

6.1 List of excipients

Succinic acid.

6.2 Incompatibilities

Although no chemical/pharmaceutical incompatibilities have been found, Fosfomycin solutions should not be mixed together with other parenteral preparations with the exception of those listed in section 6.6.

6.3 Shelf life

4 years.

Chemical and physical in-use stability of the reconstituted solution that has been produced under aseptic conditions has been demonstrated for 24 hours at 25 °C if protected from light.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C, unless reconstitution has taken place in controlled and validated aseptic conditions.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

For storage of the reconstituted solution see section 6.3.

6.5 Nature and contents of container

Clear type-II glass bottles with a rubber stopper (bromobutyl rubber) and pull-off cap containing 2 g (in 100 ml bottle), 4 g (in 100 ml bottle) or 8 g (in 250 ml bottle) of Fosfomycin, respectively, in packs of 10 bottles each.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

For single use only.

Any unused product or waste material should be disposed of in accordance with local requirements.

Preparation of the solution for infusion

In order to prepare the solution for infusion:

Fosfomycin 4 g should be dissolved in 100 ml of Water for Injections, Glucose Infusion 50mg/ml (5 %) or Glucose Infusion 100mg/ml (10 %).

A slight degree of warming occurs when the powder is dissolved.

The reconstituted solution is clear and colourless to slightly yellowish.

Displacement value

The displacement values for the reconstituted solutions are 1 ml for the 2 g pack size, 2 ml for the 4 g pack size and 4 ml for the 8 g pack size.

These volumes are equivalent to an increase of volume of 2 %. This has to be considered when preparing the final solution in case of not using the entire content of the bottle.

  1. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com

 

Fosfomycin Sodium for Injection BP 4g

PACKAGE LEAFLET: INFORMATION FOR THE USER

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor, or pharmacist or nurse.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • If you get any side effects, talk to your doctor, or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

 

What is in this leaflet:

  1. What Fosfomycin is and what it is used for
  2. What you need to know before you are given Fosfomycin
  3. How Fosfomycin is given
  4. Possible side effects
  5. How to store Fosfomycin
  6. Contents of the pack and other information

 

  1. What Fosfomycin is and what it is used for

Fosfomycin belongs to a group of medicines called antibiotics. It works by killing certain types of germs (bacteria) that cause serious infectious diseases. Your doctor has decided to treat you with Fosfomycin to help your body fight an infection. It is important that you receive effective treatment for this condition. This medicine is given as an infusion into a vein (a drip) by a doctor or a nurse.

Fosfomycin is used in adults and children to treat the following infections caused by bacteria.

  • Infections of the lung
  • Infections of the bones
  • Infections of the kidney and bladder
  • Infections of the brain (meningitis)

This medicine is used when other antibiotics cannot be used or have not worked.

This medicine can be given alone or in combination with other antibiotics.

 

  1. What you need to know before you are given Fosfomycin

In certain circumstances your doctor may decide not to give you this medicine.

Do not have Fosfomycin and tell your doctor if:

  • You are allergic (hypersensitive) to fosfomycin or any of the other

ingredients of this medicine (listed in section 6).

If you are not sure, talk to your doctor, pharmacist or nurse before having Fosfomycin.

Warnings and precautions:

Talk to your doctor, pharmacist or nurse before taking this medicine if you suffer from one of the following disorders:

  • heart problems (cardiac insufficiency), especially if digitalis medicine is taken (possible hypokalaemia)
  • high blood pressure (hypertension)
  • a certain disorder of the hormone system (hyperaldosteronism)
  • high levels of blood sodium (hypernatraemia)
  • fluid accumulation in the lungs (pulmonary oedema)
  • kidney problems. Your doctor may need to change the dose of your medicine (see section 3 of this leaflet).
  • Conditions you need to look out for Fosfomycin can cause serious side effects. These include allergic reactions and inflammation
  • of the large intestine. You must look out for certain symptoms while you are taking this medicine, to reduce the risk of any problems. See “Conditions to look out for” in Section

  1. 4. Other medicines and Fosfomycin
  • Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
  • So far, no harmful interference has been noted when this medicine is given together with other medicines.

–     Pregnancy and breast-feeding

  • If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before you are given this medicine.
  • Fosfomycin may pass to the baby in the womb or through breast milk. If you are pregnant or breast-feeding your doctor will only give you this medicine when it is clearly needed.

–     Driving and using machines

  • When Fosfomycin is given, there may be side effects such as dizziness, confusion or problems with the vision (see also section 4 “Possible Side Effects”). If these occur, you should not drive or operate machinery.

–     Important information about some of the ingredients of Fosfomycin

  • This medicine contains 14 mmol (320 mg) sodium per 1 g This is equivalent to 16 % of the recommended maximum daily dietary intake of sodium for an adult. One bottle with 2 g fosfomycin contains 28 mmol (640 mg) sodium, one bottle with 4 g fosfomycin contains 56 mmol (1280 mg) sodium and one bottle with 8 g fosfomycin contains 111 mmol (2560 mg) sodium. This should be taken in consideration if you are on a controlled sodium diet. While on treatment with this medicine, you should follow a low- salt diet to reduce your sodium intake.

–     3. How Fosfomycin is given

Administration

  • Fosfomycin is given to you into a vein (a drip) by a doctor or a nurse. The infusion will normally take 15 to 60 minutes, depending on your dose. Usually this medicine is given 2, 3 or 4 times a day.

Dosage

The dose you will be given, and the frequency of the dose will depend on:

  • The type and severity of infection you have
  • Your kidney

In children, it also depends on

  • The child’s weight
  • The child’s age

The general dosage guidelines for patients with normal kidney function are as follows:

Age/weightDaily dose
Premature neonates100 mg/kg body weight

in 2 divided doses

Neonates200 mg/kg body weight

in 3 divided doses

Infants 1-12 months (up to 10 kg body

weight)

200-300 mg/kg body weight

in 3 divided doses

Infants and children aged 1-12 years

(10-40 kg body

weight)

200-400 mg/kg body weight

in 3-4 divided doses

Adolescents aged 12-18 years and adults

(> 40 kg body

weight)

12-24 g

in 2-4 divided doses

 

Individual doses must not exceed 8 g.

If you have problems with your kidneys or require dialysis, your doctor may need to reduce your dose of this medicine.

Duration of treatment

Your doctor will decide how long your treatment should last depending on how fast your condition will improve. When

treating bacterial infections it is important to complete the full course of treatment. Even after the fever has passed and the symptoms have abated, treatment should be continued for a few days more.

Certain infections, such as infections of the bones, may require an even longer treatment period after the symptoms have subsided.

If you are given more Fosfomycin than you should

It is unlikely that your doctor or nurse will give you too much medicine. Ask them immediately if you think that you have been given too much of this medicine.

If you have any further questions on the use of this product, please ask your doctor or pharmacist.

 

  1. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Conditions to look out for

Tell your doctor straight away if you notice any of the following serious side effects – you may need urgent medical treatment:

  • Signs of a serious allergic reaction (very rare, affecting less than 1 person in 10 000). These may include: breathing or swallowing problems, sudden wheezing, dizziness, swelling of eyelids, face, lips or tongue, rash or itching.
  • Severe and persistent diarrhoea (which may be associated with abdominal

pain or fever). This may be a sign of a serious bowel inflammation. Do not take medicines against diarrhoea that inhibit the bowel movements (antiperistaltics)!

  • Yellowing of the skin or the whites of your eyes (jaundice). This can be an early sign of liver problems.
  • Confusion, muscle twitching or abnormal heart rhythm. This could be caused by high levels of blood sodium or low levels of blood potassium (common, affecting less than 1 person in 10).

Tell your doctor or nurse as soon as possible if you notice any of the following side effects:

  • Pain, burning, redness or swelling along the vein which is used during infusion of this medicine (common, affecting less than 1 person in 10).
  • You bleed or bruise more easily and get more infections as usual. This could be because you have a low number of white blood cells or blood platelets.

Other side effects can include:

Common side effects (affecting less than 1 person in 10)

  • Retching, stomach ache
  • Rash with redness of the skin

Uncommon side effects (affecting less than 1 person in 100)

  • Feeling sick, vomiting, or mild diarrhoea
  • Taste disturbances
  • Shortness of breath
  • Rash
  • Decreased appetite
  • Headache
  • Feeling of dizziness or “spinning”
  • Tiredness
  • High levels of blood liver enzymes, possibly associated with liver
  • Swelling due to fluid retention (oedema)

Rare side effects (affecting less than 1 person in 1 000)

  • Pale skin, weakness or breathlessness (possibly due to a reduction in blood cells)
  • High levels of certain white blood cells (eosinophilia), usually associated with allergic

Very rare side effects (affecting less than 1 person in 10 000)

  • Fatty liver
  • Visual impairment

Side effects with unknown frequency

  • Liver problems (hepatitis), possibly with high levels of a blood liver enzyme (gamma-glutamyltransferase)
  • Shortness of breath, wheezing or a tight feeling in the chest. These may be signs of an asthma
  • Faster heart beat
  • Low number of certain white blood cells (neutropenia)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

5. How to store Fosfomycin

  • Keep out of the reach and sight of
  • This medicine does not require any special storage
  • Do not use this medicine after the expiry date which is stated on the carton and label after “EXP”. The expiry date refers to the last day of that
  • After being mixed with solvent this medicine should be used immediately or stored in a refrigerator (at 2–8°C) protected from light for up to 24

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

 

  1. Content of the pack and other information

What Fosfomycin contains

The active substance is fosfomycin. Each ml of the solution for infusion contains 40 mg of fosfomycin.

  • Each bottle of Fosfomycin 4 g with 5.38 g of powder for solution in 100 ml solvent contains 5.28 g disodium fosfomycin, corresponding to 4 g fosfomycin and

1.28 g sodium.

The other ingredient is succinic acid.

What Fosfomycin looks like and contents of the pack

This medicine is a white to cream-coloured powder for solution for infusion. The solution for infusion is clear and colourless to slightly yellowish.

It is packed in clear glass bottles (type I) with a rubber stopper (bromobutyl rubber) and pull-off cap.

Three sizes of vials are available:

  • bottles with 4 g fosfomycin
  • Each pack contains 10

 

  1. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    Mumbai, India
    Unit No. 214.Old Bake House,
    Maharashtra chambers of Commerce Lane,
    Fort, Mumbai – 400001
    at:Gujarat, INDIA.
    Customer Service and Product Inquiries:
    1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
    Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
    E-mail: tajgroup@tajpharma.com