Vancocin Matrigel 125 mg Hard capsules.

Each capsule contains 125 mg vancomycin (as hydrochloride)

For full list of excipients, see section 6.1

Capsules, hard

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

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.

For oral administration

Either the Matrigel capsules or the contents of the 500 mg vial for the 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.

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.

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.

Hypersensitivity to vancomycin.

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.

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

Usage in 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.

Usage in nursing mothers: Vancomycin hydrochloride is excreted in human milk. Caution should be exercised when vancomycin is administered to a nursing woman.

None known

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.

Treatment of Overdosage

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.

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.

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 μg/ml. With doses of 2 g daily, concentration of 3,100 mg/kg can be found in the faeces and levels of <1 μg/ml can be found in the serum of patients with normal renal function who have pseudomembranous colitis.

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

Macrogol 6000

Capsule shell

Gelatin

Indigo carmine (E132)

Red iron oxide (E172

Yellow iron oxide (E172)

Titanium dioxide (E171)

Printing ink

Shellac

Soya lecithin

Dimeticone

Iron oxide red (E172)

Not applicable.

Two years.

Do not store above 25°C. Store in the original package.

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.

No special requirements.

Flynn Pharma Limited

Alton House

4 Herbert Street

Dublin 2

Republic of Ireland

PL 13621/0030

Date of first authorisation: 25 September 1985

Date of last renewal of authorisation: 15^th October 2005

Approved July 2008