FOMICYT Powder for solution for infusion Ref.[6865] Active ingredients: Fosfomycin

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 (320 mg) sodium. One bottle with 2 g of 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 of fosfomycin contains 111 mmol (2560 mg) 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.

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.

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.

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).

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

Blood and lymphatic system disorders

Rare: Aplastic anaemia, eosinophilia

Frequency not known: Agranulocytosis, granulocytopenia, leucopenia, pancytopenia, thrombocytopenia, neutropenia

Immune system disorders

Very rare: Anaphylactic shock (see section 4.4)

Metabolism and nutrition disorders

Uncommon: Decreased appetite, hypernatraemia and/or hypokalaemia (see section 4.4), oedema

Psychiatric disorders

Frequency not known: Confusion

Nervous system disorders

Uncommon: Dysgeusia, headache

Eye disorders

Very rare: Visual impairment

Ear and labyrinth disorders

Uncommon: Vertigo

Cardiac disorders

Frequency not known: Tachycardia

Respiratory, thoracic and mediastinal disorders

Uncommon: Dyspnoea

Frequency not known: Asthmatic attack

Gastrointestinal disorders

Common: Retching, stomach ache

Uncommon: Nausea, vomiting, diarrhoea

Frequency not known: Pseudomembranous colitis (see section 4.4)

Hepatobiliary disorders

Uncommon: Blood alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase increased (transient)

Very rare: Fatty liver (completely reversible after discontinuation of fosfomycin)

Frequency not known: Hepatitis, cholestatic hepatitis, icterus

Skin and subcutaneous tissue disorders

Uncommon: Rash

Frequency not known: Angioedema, facial oedema, pruritus, urticaria

General disorders and administration site conditions

Common: Injection site phlebitis

Uncommon: Fatigue

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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

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