VANCOCIN CP INTRAVENOUS INJECTION (VANCOMYCIN)

Hypersensitivity reactions Severe and occasionally fatal hypersensitivity reactions are possible (see sections 4.3 and 4.8). In the event of hypersensitivity reactions, vancomycin treatment must be discontinued immediately and emergency measures instituted. In patients receiving vancomycin over a prolonged period or concomitantly with other products that may cause neutropenia or agranulocytosis, the leukocyte count should be monitored at regular intervals. All patients receiving vancomycin should undergo periodic haematological tests, urinalysis and liver and renal function tests. Vancomycin should be used with caution in patients with allergic reactions to teicoplanin, as cross-hypersensitivity may occur, including fatal anaphylactic shock. Spectrum of antibacterial activity Vancomycin has a spectrum of antibacterial activity limited to gram-positive organisms. It is not suitable for use as a single agent for the treatment of certain types of infection unless the pathogen has already been identified and is known to be susceptible, or there is a high suspicion that the most likely pathogen or pathogens are suitable for treatment with vancomycin. The rational use of vancomycin should take into account the bacterial spectrum of activity, the safety profile and the standard of antibacterial therapy for the treatment of the individual patient. Ototoxicity Ototoxicity, which may be transient or permanent (see section 4.8), has been reported in patients with pre-existing deafness who received high intravenous doses of vancomycin, or who were concomitantly treated with another ototoxic product such as aminoglycosides. Vancomycin should also be avoided in patients with pre-existing hearing loss. Deafness may be preceded by tinnitus. Experience with other antibiotics suggests that deafness may be progressive despite discontinuation of treatment. To reduce the risk of ototoxicity, blood levels should be assessed regularly and periodic monitoring of auditory function is recommended. Elderly patients are particularly susceptible to hearing damage. Monitoring of vestibular and auditory function in elderly patients should be performed during and after treatment. Concomitant or subsequent administration of other ototoxic agents should be avoided. Infusion-related reactions Rapid bolus administration (e.g. over a few minutes) may be associated with exaggerated hypotension (including shock and, more rarely, cardiac arrest), a histamine-like reaction and a maculopapular or erythematous rash (“red man syndrome” or “red neck syndrome”). Vancomycin should be administered as a slow infusion in a dilute solution (2.5 to 5.0 mg/mL) at a rate no greater than 10 mg/min and over a period of at least 60 minutes to prevent reactions associated with rapid infusion. Stopping the infusion usually leads to rapid resolution of these reactions. The frequency of infusion-related reactions (hypotension, flushing, erythema, urticaria and pruritus) increases with the concomitant administration of anaesthetics (see section 4.5). This may be limited by administering vancomycin by infusion over at least 60 minutes before the induction of anaesthesia. Severe cutaneous adverse reactions (SCAR) Severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported in association with vancomycin treatment (see section 4.8). Most of these reactions occurred within a few days to eight weeks after the start of vancomycin treatment. When prescribing the drug, patients should be informed of the signs and symptoms and carefully monitored for the possible occurrence of a skin reaction. If signs and symptoms suggestive of these reactions appear, vancomycin must be discontinued immediately and alternative treatment should be considered. If a patient has developed a SCAR during vancomycin treatment, vancomycin treatment must never be restarted. Administration site reactions Pain and thrombophlebitis may occur in many patients receiving vancomycin intravenously and may occasionally be severe. The frequency and severity of thrombophlebitis can be minimised by slow administration of the medicinal product as a dilute solution (see section 4.2) and by regularly rotating the infusion sites. The efficacy and safety of vancomycin have not been established for the intrathecal, intralumbar and intraventricular routes of administration. Parenteral administration Nephrotoxicity Vancomycin should be administered with caution in patients with renal impairment, including anuria, as the potential for toxic effects is much higher with prolonged high blood concentrations. The risk of toxicity is increased by high blood concentrations or prolonged treatment. Regular monitoring of vancomycin blood levels is indicated during high-dose therapy and prolonged administration, particularly in patients with renal impairment or hearing impairment, as well as during concomitant administration of nephrotoxic or ototoxic medicinal products (see sections 4.2 and 4.5). Eye disorders Vancomycin is not authorised for intracameral or intravitreal administration, including prophylaxis of endophthalmitis. Following intracameral or intravitreal administration of vancomycin during or after cataract surgery, isolated cases of haemorrhagic occlusive retinal vasculitis (HORV), including permanent loss of vision, have been observed. Paediatric population Current intravenous dosing recommendations for the paediatric population, particularly for children under 12 years of age, may lead to subtherapeutic vancomycin levels in a substantial number of children. However, the safety of increased vancomycin dosing has not been adequately evaluated and, in general, doses higher than 60 mg/kg/day cannot be recommended. Vancomycin should be administered with particular caution in premature neonates and young infants because of renal immaturity and the possible increase in serum vancomycin concentrations. Vancomycin blood concentrations should therefore be closely monitored in these children. Concomitant administration of vancomycin and anaesthetics has been associated in children with erythema and flushing resembling a histamine reaction. Similarly, concomitant use with nephrotoxic medicinal products such as aminoglycoside antibiotics, NSAIDs (e.g. ibuprofen for closure of patent ductus arteriosus) or amphotericin B is associated with an increased risk of nephrotoxicity (see section 4.5), and more frequent monitoring of serum vancomycin levels is therefore indicated. Use in elderly patients The natural decline in glomerular filtration with advancing age may lead to increased serum concentrations if the dose is not adjusted (see section 4.2). Interaction with anaesthetics Anaesthetic-induced myocardial depression may be enhanced by vancomycin. During anaesthesia, the dose must be well diluted and administered slowly with careful cardiac monitoring. To allow postural adaptation, changes in position should be made only after the infusion has been completed (see section 4.5). Pseudomembranous enterocolitis In the case of severe persistent diarrhoea, the possibility of pseudomembranous enterocolitis, which could be life-threatening, must be considered (see section 4.8). Antidiarrhoeals must not be administered. Superinfection Prolonged administration of vancomycin may result in overgrowth of non-susceptible organisms. Careful monitoring of the patient is essential. If superinfection occurs during treatment, appropriate measures should be taken. Oral administration Intravenous administration of vancomycin is not effective for the treatment of infections caused by Clostridium difficile. For this indication, vancomycin should be administered orally. Testing for Clostridium difficile colonisation or determination of toxins is not recommended in children under 1 year of age because of the high rate of asymptomatic colonisation, unless severe diarrhoea is present in children with risk factors for stasis such as Hirschsprung’s disease, operated anal atresia or other severe disorders of intestinal motility. An alternative aetiology should always be sought, and enterocolitis caused by Clostridium difficile should be confirmed. Potential for systemic absorption Absorption may be enhanced in patients with inflammatory disorders of the intestinal mucosa or with pseudomembranous colitis caused by Clostridium difficile. In these patients there is a risk of developing adverse reactions, particularly if renal impairment is concurrently present. The greater the degree of renal impairment, the higher the risk of developing adverse reactions associated with parenteral administration of vancomycin. In patients with inflammatory disease of the intestinal mucosa, monitoring of serum vancomycin concentrations must be carried out. Nephrotoxicity Repeated monitoring of renal function is necessary when treating patients with existing renal impairment or patients undergoing concomitant treatment with aminoglycosides or other nephrotoxic medicinal products. Ototoxicity Repeated auditory function testing may help minimise the risk of ototoxicity in patients with existing hearing loss or in patients treated concomitantly with ototoxic medicinal products such as aminoglycosides. Interaction with antiperistaltic agents and proton pump inhibitors The administration of antiperistaltic agents should be avoided, and the administration of proton pump inhibitors should be reassessed. Development of bacterial resistance Oral administration of vancomycin increases the possibility of vancomycin-resistant enterococci developing in the gastrointestinal tract. For this reason, cautious oral use of vancomycin is recommended. Cardiovascular and cerebrovascular effects Cases of Kounis syndrome have been reported in patients treated with vancomycin. Kounis syndrome has been defined as cardiovascular symptoms secondary to an allergic or hypersensitivity reaction associated with narrowing of the coronary arteries and potentially leading to myocardial infarction.