Vancomycin 125mg Capsules Hard
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Vancomycin 125mg Capsules, Hard.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 128.15mg of vancomycin hydrochloride equivalent to 125mg vancomycin base.
For a full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Capsule(s), hard.
Opaque blue and opaque brown hard capsule(s)
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Vancomycin may be used orally for the treatment of staphylococcal 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
For oral administration.
Adults, adolescents 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 (12 years or under):
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.
Vancomycin Capsules may not be suitable for children below the age of 6 years. Other formulations (e.g. solution) of Vancomycin are available and should be used instead
The absorption of vancomycin is not affected by food intake.
4.3 Contraindications
Vancomycin Capsules is contraindicated in patients with known hypersensitivity to vancomycin or any of the excipients
4.4 Special warnings and precautions for use
Precautions
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. The risk may be increased in patients with impaired renal function.
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 (see package insert accompanying the intravenous preparation). 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 including fungi. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.
4.5 Interaction with other medicinal products and other forms of interaction
No interactions have been reported for orally administered vancomycin. In patients with severe renal impairment and severe colitis systemic absorption may occur resulting in a risk for interactions that are normally only seen after parenteral administration. For example, parenteral administration of vancomycin and anaesthetics may cause erythema and anaphylactic reactions.
Some antibiotics were rarely reported to reduce the effect of oral contraceptives by interfering with the bacterial hydrolysis of conjugated steroids in the intestine and thus reabsorption of unconjugated steroid. This would lower the plasma levels of active steroid. This unusual interaction would occur in women with high excretion of conjugated steroids in bile.
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: Reproduction toxicological studies on animals do not suggest any effects on the development of the embryo, foetus or gestation period (see section 5.3).
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
Vertigo and dizziness have been reported rarely, and may affect the ability to drive and to use machines
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').
Blood and the lymphatic system disorder:
Rare (> 10,000 to <1/1,000): Thrombocytopaenia, reversible neutropenia,
reversible agranulocytoses, eosinophilia.
Immune system disorders:
Rare (> 10,000 to <1/1,000): Anaphylactic reactions, hypersensitivity reactions.
Ear and labyrinth disorders:
Rare (> 10,000 to <1/1,000): Tinnitus, dizziness, vertigo.
Very rare (<1/10,000)): Transient or permanent loss of hearing.
Cardiac disturbances
Very rare (<1/10,000): Cardiac arrest
Vascular disorders:
Common (>1/100 to <1/10): Decrease in blood pressure.
Rare (> 10,000 to <1/1,000): Vasculitis.
Respiratory, thoracic and mediastinal disorders:
Common (>1/100 to <1/10): Dyspnoea, stridor.
Gastrointestinal Disorders:
Rare (> 10,000 to <1/1,000): Nausea.
Very rare (<1/10,000) Pseudomembranous enterocolitis.
Skin and subcutaneous tissue disorders:
Common (>1/100 to <1/10): Exanthaema and mucosal inflammation, pruritus,
urticaria.
Rare (> 10,000 to <1/1,000): _IgA induced bullous dermatitis
Very rare (<1/10, 000): Exfoliative dermatitis, Stevens-Johnson syndrome, Lyell’s syndrome, vasculitis, IgA induced bullous dermatitis
Renal and urinary disorders:
Common (>1/100 to <1/10): Renal insufficiency manifested primarily by
increased serum creatinine or serum urea concentrations.
Rare (> 10,000 to <1/1,000): Interstitial nephritis, acute renal failure.
General disorders and administration site conditions:
Common (>1/100 to <1/10): Redness of the upper body and the face. Pain and
spasm of the chest and back muscles.
Rare (> 10,000 to <1/1,000): Anaphylactic reactions, drug fever, shivering.
Ototoxicity has primarily been reported in patients given high doses, or concomitant treatment with other ototoxic medicinal products, or had pre-existing reduction in kidney function or hearing.
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 Website: www.mhra.gov.uk/yellowcard
4.9 Overdose
Toxicity: Limited experience in overdose, however, 500 mg IV given to a 2-year-old lead to lethal intoxication. 56 g spread over 10 days to an adult caused renal insufficiency.
Signs and symptoms: overdose may cause nausea, vomiting, epigastric discomfort and diarrhoea.
Treatment: supportive treatment is recommended, with maintenance of glomerular filtration. Vancomycin is not adequately eliminated by dialysis. It has been reported that haemofiltration and haemoperfusion with polysulfone resin has limited benefit.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: other antibacterials; glycopeptides. ATC Code: JO1XA01.
Mechanism of action: the bactericidal action of vancomycin is principally due to an inhibition of cell wall biosynthesis. It also affects the permeability of the bacterial cell membrane and inhibits RNA synthesis.
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.
Mechanism(s) of resistance
Acquired resistance to glycopeptides is based on acquisition of various van gene complexes. Van genes have rarely been found in Staphylococcus aureus, where changes in cell wall structure result in “intermediate” susceptibility, which is most commonly heterogeneous.
There is no cross-resistance between vancomycin and other antibiotics but crossresistance with other glycopeptide antibiotics, such as teicoplanin, does occur. Secondary development of resistance during therapy is rare.
In some countries, increasing cases of resistance are observed particularly in enterococci; multi-resistant strains of Enterococcus faecium are especially alarming.
5.2 Pharmacokinetic properties
Orally administered vancomycin does not usually enter the systemic circulation even when inflammatory lesions are present. Measurable serum concentrations may infrequently occur in patients with active C.difficile-induced pseudomembranous colitis, and, in the presence of renal impairment, the possibility of accumulation exists.
Vancomycin is poorly absorbed from the gastro-intestinal tract. During multiple dosing of 250mg 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%.
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 pg/ml. With doses of 2 g daily, concentrations of>3, 100 mg/kg can be found in the feces, and levels of <1 pg/ml can be found in the serum of patients with normal renal function who have pseudomembranous colitis.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology and repeated dose toxicity.
Limited data on mutagenic effects show negative results, long-term studies in animals regarding a carcinogenic potential are not available. In teratogenicity studies, where rats and rabbits received doses approximately corresponding to the human dose based on body surface (mg/m2), no direct or indirect teratogenic effects were observed.
Animal studies of the use during the perinatal/postnatal period and regarding effects on fertility are not available.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Each hard capsule contains the following excipient: polyethylene glycol
Capsule shell components Gelatin
FD & C blue no.2 lake (E132)
Iron oxide red (E172 Iron oxide yellow (E172)
Purified water Sodium lauryl sulphate Titanium dioxide (E171)
6.2 Incompatibilities
Not applicable
6.3 Shelf life
36 months
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions .
Keep blisters in the outer carton to protect from moisture
6.5 Nature and contents of container
Clear transparent PVC/ACLAR* film and Aluminium lidding foil.
Blister packs of 10, 14, 15, 20, 28, 30, 56, 60, 84, 90 and 112 capsules.
Not all pack sizes may be marketed
6.6 Special precautions for disposal
No special requirements
Any unused product or waste material should be disposed of in accordance with local requirements
7 MARKETING AUTHORISATION HOLDER
Morningside Healthcare Limited,
115 Narborough Road, Leicester,
LE30PA UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 20117/0149
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
16/01/2014
10 DATE OF REVISION OF THE TEXT
16/01/2014