SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Vancocin Matrigel 125mg Hard capsules.

2.    QUALITATIVE AND QUANTITATIVE    COMPOSITION

Each capsule contains 125mg vancomycin (as hydrochloride)

For full list of excipients, see section 6.1.

3.    PHARMACEUTICAL FORM

Capsules, hard

Dark blue and peach hard capsules, imprinted with 3125 in red ink

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Vancomycin may be used orally for the treatment of staphylococcai enterocolitis and pseudomembranous colitis due to Clostridium difficile.

Vancomycin is not significantly absorbed from the normal gastro-intestinal tract and is therefore not effective by the oral route for other types of infection. Intravenous administration may be used concomitantly if required.

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

4.2 Posology and method of administration

Posology

Either the Matrigel capsules or the contents of the 500 mg vial for parenteral administration may be used.

Adults and the elderly: The usual daily dose is 500 mg in divided doses for 7 to 10 days, although up to 2 g/day, in three or four divided doses, have been used in severe cases. The total daily dosage should not exceed 2 g.

Oral solution: The contents of the 500 mg vial for parenteral administration may be used and either given to the patient to drink, or administered by nasogastric tube. Mix thoroughly to dissolve. Common flavouring syrups may be added to the solution at the time of administration to improve the taste.

Paediatric population

Children: The usual daily dose is 40 mg/kg in three or four divided doses for 7 to 10 days. The total daily dosage should not exceed 2 g.

Method of administration

For oral administration.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section

6.1.

4.4. Special warnings and precautions for use

Clinically significant serum concentrations have been reported in some patients who have taken multiple oral doses of vancomycin for active C. difficile'-induced pseudomembranous colitis. Therefore, monitoring of serum concentrations may be appropriate in these patients.

Some patients with inflammatory disorders of the intestinal mucosa may have significant systemic absorption of vancomycin and, therefore, may be at risk for the development of adverse reactions associated with the parenteral administration of vancomycin. The risk is greater in patients with renal impairment. It should be noted that the total systemic and renal clearances of vancomycin are reduced in the elderly.

Ototoxicity has occurred in patients receiving vancomycin. It may be transient or permanent. It has been reported mostly in patients who have been given excessive intravenous doses, have an underlying hearing loss, or are receiving concomitant therapy with an ototoxic agent such as an aminoglycoside. Serial tests of auditory function may be helpful in order to minimise the risk of ototoxicity.

When treating patients with underlying renal dysfunction or patients receiving concomitant therapy with an aminoglycoside, serial monitoring of renal function should be performed.

Prolonged use of vancomycin may result in the overgrowth of non-susceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.

4.5. Interactions with other medicinal products and other forms of interaction

Concurrent and/or sequential systemic or topical use of other potentially ototoxic and/or nephrotoxic drugs requires careful monitoring.

4.6    Fertility, pregnancy and lactation

Pregnancy

Teratology studies have been performed at 5 times the human dose in rats and 3 times the human dose in rabbits, and have revealed no evidence of harm to the foetus due to vancomycin. In a controlled clinical study, the potential ototoxic and nephrotoxic effects of vancomycin hydrochloride on infants were evaluated when the drug was administered to pregnant women for serious staphylococcal infections complicating intravenous drug abuse. Vancomycin hydrochloride was found in cord blood. No sensorineural hearing loss or

nephrotoxicity attributable to vancomycin was noted. One infant, whose mother received vancomycin in the third trimester, experienced conductive hearing loss that was not attributable to vancomycin. Because vancomycin was administered only in the second and third trimesters, it is not known whether it causes foetal harm. Therefore vancomycin should be given to a pregnant woman only if clearly needed.

Breast-feeding

Vancomycin hydrochloride is excreted in human milk.

Caution should be exercised when vancomycin is administered to a nursing woman.

4.7    Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

Since vancomycin is not usually significantly absorbed from the gastro-intestinal tract, the toxicity encountered with parenteral therapy is unlikely to occur after oral administration (but see ‘Precautions’).

Nephrotoxicity: Rarely, renal failure, principally manifested by increased serum creatinine or blood urea concentrations, have been observed, especially in patients given large doses of intravenously administered vancomycin. Rare cases of interstitial nephritis have been reported. Most occurred in patients who were given aminoglycosides concomitantly or who had pre-existing kidney dysfunction. When vancomycin was discontinued, azotaemia resolved in most patients.

Ototoxicity: Hearing loss associated with intravenously administered vancomycin has been reported. Most of these patients had kidney dysfunction, pre-existing hearing loss, or concomitant treatment with an ototoxic drug. Vertigo, dizziness and tinnitus have been reported rarely.

Haematological: Reversible neutropenia, usually starting one week or more after onset of intravenous therapy or after a total dose of more than 25g, Neutropenia appears to be promptly reversible when vancomycin is discontinued. Thrombocytopenia and reversible agranulocytosis (granulocyte count less than 5oo/mm3) have been reported rarely. Eosinophilia has been reported rarely.

Miscellaneous: Hypersensitivity reactions, anaphylaxis, chills, drug fever, hypotension, wheezing, dyspnoea, urticaria, pruritus, flushing of the upper body (‘red neck syndrome’), pain, muscle spasm of the chest and back, nausea and rashes, including exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis and rare cases of vasculitis.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continues 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 Website: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is poorly removed by dialysis. Haemofiltration and haemoperfusion with Amberlite resin XAD-4 have been reported to be of limited benefit.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antibiotics, ATC Code: A07AA09

Vancomycin is a tricyclic glycopeptide antibiotic derived from Amycolatopsis orientalis. The bacterial action of vancomycin results primarily from inhibition of cell-wall biosynthesis. In addition, vancomycin may alter bacterial cell membrane permeability and RNA synthesis. There is no cross-resistance between vancomycin and other classes of antibiotics.

Orally administered vancomycin is active against C. difficile (e.g. toxigenic strains implicated in pseudomembranous enterocolitis). It is also active against staphylococci, including Staphylococcus aureus. Vancomycin is not active in vitro against Gram-negative bacilli, mycobacteria or fungi.

5.2. Pharmacokinetic properties

Vancomycin is poorly absorbed from the gastro-intestinal tract. During multiple dosing of 250 mg every 8 hours for 7 doses, faecal concentrations of vancomycin, in volunteers, exceeded 100mg/kg in the majority of samples.

No blood concentrations were detected and urinary recovery did not exceed 0.76%.

Orally administered vancomycin does not usually enter the systemic circulation even when inflammatory lesions are present. Measurable serum concentrations may occur infrequently in patients with active C. difficile-induced pseudomembranous colitis and, in the presence of renal impairment, the possibility of accumulation exists.

Administration of vancomycin oral solution, 2 g daily for 16 days to anephric patients with no inflammatory bowel disease, gave serum levels of <0.66 ^g/ml. With doses of 2 g daily, concentration of 3,100 mg/kg can be found in the faeces and levels of <1 ^g/ml can be found in the serum of patients with normal renal function who have pseudomembranous colitis.

5.3. Pre-clinical Safety Data

There are no preclinical data of relevance to the prescriber in addition to that summarised in other sections of the Summary of Product Characteristics.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Capsule contents Macrogol 6000

Capsule shell Gelatin

Indigo carmine (E132)

Red iron oxide (E172)

Yellow iron oxide (E172)

Titanium dioxide (E171)

Printing ink Shellac

Propylene glycol Potassium hydroxide Red iron oxide (E172)

6.2.    Incompatibilities

Not applicable.

6.3.    Shelf Life

Two years.

6.4 Special precautions for storage

Do not store above 25°C. Store in the original blister in order to protect from moisture.

6.5. Nature and contents of container

AL/UPVC/Aclar blister packs of 20 capsules (2 strips of 10 capsules) or 28 capsules (4 strips of 7 capsules).

Not all pack sizes may be marketed.

6.6    Special precautions for disposal

No special requirements for disposal.

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

7.    MARKETING AUTHORISATION HOLDER

Flynn Pharma Limited Alton House 4 Herbert Street Dublin 2 Ireland

8.    MARKETING AUTHORISATION NUMBER(S)

PL 13621/0030

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 26 September 1985 Date of latest renewal: 06January 2006

10 DATE OF REVISION OF THE TEXT

10/09/2015