VancoAvenir

/ BioAvenir Ltd.

Therapeutic indications for intravenous and oral administration are different. Both administration routes could not be commuted.
Intravenous administration:
Solution concentrations of no more than 5 mg/ml are recommended. In selected patients in need of fluid restriction, solution concentration up to 10 mg/ml may be used; use of such higher concentrations may increase the risk of infusion-related events. Infusions should be given over at least 60 minutes. In adults, if doses exceeding 500 mg are used, a rate of infusion of no more than 10 mg/min is recommended. Infusion-related adverse events are related to both concentration and rate of administration of vancomycin. The duration of treatment is guided by the severity of the infection and its clinical and bacteriological progression.
Adults, adolescents and children over 12 years old:
The recommended daily intravenous dose is 2000 mg (2g), divided into 500 mg doses administered every 6 hours or (1g) 1000mg every 12 hours. Each dose should be administered at no more than 10 mg/min or over a period of at least 60 minutes, whichever is longer.
For bacterial endocarditis, the generally accepted regimen is 1000 mg of vancomycin intravenously every 12 hours for 4 weeks either alone or in combination with other antibiotics (gentamicin plus rifampin, gentamicin, streptomycin).
Enterococcal endocarditis is treated for 6 weeks with vancomycin in combination with an aminoglycoside – according to national recommendations.
Children 1 month to 12 years old:
The recommended intravenous dose is 10 mg/kg, every 6 hours. Each dose should be administered over a period of at least 60 minutes.
Infants and newborn:
The recommended initial dose is 15 mg/kg, followed by 10 mg/kg every 12 hours during the first week of life, and every 8 hours after that age and up to 1 month of age. Each dose should be administered over at least 60 minutes. Close monitoring of serum concentrations of vancomycin is recommended.
Elderly patients:
Lower maintenance doses than for adults may be required due to the age –related reduction in renal function.
Obese patients:
Modification of usual daily doses may be required.
Patients with impaired hepatic function:
There is no evidence that the dose has to be reduced in patients with impaired hepatic function.
Patients with impaired renal function:
Dosage adjustment must be made in patients with impaired renal function. In order to optimize dosage, serum vancomycin concentrations should be measured by means of microbiological assay, radioimmunoassay, fluorescence polarization immunoassay, fluorescence immunoassay or high pressure liquid chromatography.
Oral administration:
Treatment of colitis due to C. difficile:
Adults: The usual daily dose is 0,5g to 2 g given in 4 divided doses (125 mg to 500 mg per dose) for 7 to 10 days.
Children: The usual daily dose is 40 mg/kg/day given in 4 divided doses, up to a maximum of 250 mg/dose, for 7 to 10 days.
See prescribing information for full details.

Treatment of severe or serious infections due to susceptible strains of methicillin – resistant (beta-lactam-resistant) staphylococci.
It is also indicated for administration to penicillin-allergic patients as well patients who have failed to respond to or who cannot receive other drugs including cephalosporins or penicillins and for infections due to vancomycin-susceptible organisms that are resistant to other antimicrobial drugs.
Vancomycin hydrochloride is indicated for first-line therapy when methicillin-resistant staphylococci are suspected but when susceptibility data become available appropriate therapy should be instituted.
Vancomycin hydrochloride is effective in the treatment of staphylococcal endocarditis as well as in other infections due to staphylococci including lower respiratory tract infections septicemia skin and skin – stucture infection and bone infections.
Antibiotic therapy is as an adjunct to appropriate surgical measures when staphylococcal infections are purulent and localized.
For endocarditis due to Streptococcus viridans or Streptococcus bovis vancomycin hydrochloride has been shown to be effective in combination with an aminoglycoside. Vancomycin hydrochloride has been shown to be effective only in combination with an aminoglycoside for endocarditis due to enterococci (eg Enterococcus fecalis).
Vancomycin hydrochloride has been shown to be effective for the treatment of diphtheroid endocareditis. In early-onset prosthetic valve endocarditis caused by Staphylococcus epidermidis or diptheroids vancomycin hydrochloride has been administered successfully in combination with either rifampin an aminoglycoside or combined with both drugs.
Bacteriologic cultures of specimens should be obtained for isolation and identification of causative organisms and determination of susceptibilities to vancomycin hydrochloride.
Oral Therapy Vancomycin hydrochloride injection may be given orally for the treatment of antibiotic associated Pseudomembranous colitis due to Staphylococcus enterocolitis and Clostridium difficile.
Vancomycin hydrochloride is not effective orally when administered for other types of infection.

Patients with known hypersensitivity to the active substance (vancomycin).Vancomycin should not be administered intramuscularly due to the risk of necrosis at the site of administration.

Hypersensitivity reactions:
Serious and occasionally fatal hypersensitivity reactions are possible. In case of hypersensitivity reactions, treatment with vancomycin must be discontinued immediately and the adequate emergency measures must be initiated.
In patients receiving vancomycin over a longer-term period or concurrently with other medications which may cause neutropenia or agranulocytosis, the leukocyte count should be monitored at regular intervals. All patients receiving vancomycin should have periodic haematologic studies, urine analysis, liver and renal function tests.
Vancomycin should be used with caution in patients with allergic reactions to teicoplanin, since cross hypersensitivity, including fatal anaphylactic shock, may occur.
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 some types of infections unless the pathogen is already documented and known to be susceptible or there is a high suspicion that the most likely pathogen(s) would be suitable for treatment with vancomycin.
The rational use of vancomycin should take into account the bacterial spectrum of activity, the safety profile and the suitability of standard antibacterial therapy to treat the individual patient.
Ototoxicity:
Ototoxicity, which may be transitory or permanent has been reported in patients with prior deafness, who have received excessive intravenous doses, or who receive concomitant treatment with another ototoxic active substance such as an aminoglycoside. Vancomycin should also be avoided in patients with previous hearing loss. Deafness may be preceded by tinnitus. Experience with other antibiotics suggests that deafness may be progressive despite cessation of treatment. To reduce the risk of ototoxicity, blood levels should be determined periodically and periodic testing of auditory function is recommended.
The elderly are particularly susceptible to auditory damage. Monitoring of vestibular and auditory function in the elderly should be carried out during and after treatment. Concurrent or sequential use of other ototoxic substances should be avoided.
Infusion-related reactions:
Rapid bolus administration (e.g., over several minutes) may be associated with exaggerated hypotension, shock and, rarely, cardiac arrest, histamine like responses and maculopapular or erythematous rash (“red man’s syndrome” or “red neck syndrome”). So vancomycin should be infused slowly in a diluted solution (2.5 to 5.0mg/ml) at a rate not greater than 10 mg/min and over a period of not less than 60 minutes to avoid rapid infusion-related reactions. Stopping the infusion usually results in a prompt cessation of these reactions. The frequency of infusion-related reactions (including hypotension, flushing, erythema, urticaria and pruritus) increases with the concomitant administration of anaesthetic agents. This may be reduced by administering vancomycin by infusion over at least 60 minutes, before anaesthetic induction.
Severe cutaneous adverse reactions (SCARs):
Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP), which can be life-threatening or fatal, have been reported in association with vancomycin treatment. Most of these reactions occurred within a few days and up to eight weeks after commencing treatment with vancomycin.
At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, vancomycin should be withdrawn immediately and an alternative treatment considered. If the patient has developed a SCAR with the use of vancomycin, treatment with vancomycin must not be restarted at any time.
Administration site related reactions:
Pain and thrombophlebitis may occur in many patients receiving intravenous vancomycin and are occasionally severe. The frequency and severity of thrombophlebitis can be minimized by administering the medicinal product slowly as a dilute solution and by changing the sites of infusion regularly.
The efficacy and safety of vancomycin has not been established for the intrathecal, intralumbar and intraventricular routes of administration. The administration of vancomycin by intraperitoneal injection during continuous ambulatory peritoneal dialysis has been associated with a syndrome of chemical peritonitis.
Nephrotoxicity:
Vancomycin should be used with care in patients with renal insufficiency, including anuria, as the possibility of developing toxic effects is much higher in the presence of prolonged high blood concentrations. The risk of toxicity is increased by high blood concentrations or prolonged therapy.
Regular monitoring of the blood levels of vancomycin is indicated in high dose therapy and longer-term use, particularly in patients with renal dysfunction or impaired faculty of hearing as well as in concurrent administration of nephrotoxic or ototoxic substances, respectively.
Eye disorders:
Vancomycin is not authorized for intracameral or intravitreal use, including prophylaxis of endophthalmitis.
Hemorrhagic occlusive retinal vasculitis (HORV), including permanent loss of vision, have been observed in individual cases following intracameral or intravitreal use of vancomycin during or after cataract surgery.
Paediatric population:
The current intravenous dosing recommendations for the paediatric population, in particular for children below 12 years of age, may lead to sub-therapeutic vancomycin levels in a substantial number of children. However, the safety of increased vancomycin dosing has not been properly assessed and higher doses than 60 mg/kg/day cannot be generally recommended.
Vancomycin should be used with particular care in premature neonates and young infants, because of their renal immaturity and the possible increase in the serum concentration of vancomycin. The blood concentrations of vancomycin should therefore be monitored carefully in these children. Concomitant administration of vancomycin and anaesthetic agents has been associated with erythema and histamine-like flushing in children and anaphylactoid reactions. If vancomycin has to be administered in surgical prophylaxis, it is recommended that the anaesthetic agents be administered after the vancomycin infusion has been completed.
. Similarly, concomitant use with nephrotoxic agents 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 and therefore more frequent monitoring of vancomycin serum levels and renal function is indicated.
Use in the elderly:
The natural decrement of glomerular filtration with increasing age may lead to elevated vancomycin serum concentrations if dosage is not adjusted.
Drug interactions with anaesthetic agents:
Anaesthetic induced myocardial depression may be enhanced by vancomycin. During anaesthesia, doses must be well diluted and administered slowly with close cardiac monitoring. Position changes should be delayed until the infusion is completed to allow for postural adjustment.
Pseudomembranous enterocolitis:
In case of severe persistent diarrhoea the possibility of pseudomembranous enterocolitis that might be life-threatening has to be taken into account. Anti-diarrhoeic medicinal products must not be given.
Superinfection:
Prolonged use of vancomycin may result in the overgrowth
prolonged use of vancomycin may result in the overgrowth of nonsusceptible microorganisms, principally fungi. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.
Reversible neutropenia has been reported. Patients undergoing prolonged therapy with vancomycin or those who are receiving concomitant drugs that may cause neutropenia should have periodic monitoring of the leukocyte count.

Common: Flushing of the upper body (“red man syndrome”), decrease in blood pressure, dyspnea, stridor, exanthema and mucosal inflammation, pruritus, urticarial, renal insufficiency manifested primarily by increased serum creatinine and serum urea, phlebitis, redness of the upper body and face.
see prescribing information for full details.

Other potentially nephrotoxic or ototoxic medications:
Concomitant or sequential administration of vancomycin and other potentially ototoxic or nephrotoxic medicinal products may increase the ototoxicity or nephrotoxicity. Nephrotoxic medicinal products may include iodine-containing contrast media, aminoglycoside antibiotics, platinum-based chemotherapy agents, methotrexate at high doses, piperacilline/tazobactam and some antiviral drugs such as pentamidine, foscarnet, aciclovir, ganciclovir, famciclovir, valaciclovir, valganciclovir, ciclosporin or tacrolimus. Aminoglycoside antibiotics, platinum-based chemotherapy agents and some diuretics could be ototoxic drugs. The patient should be closely monitored, especially in case of concomitant administration of aminoglycoside antibiotics. The maximum dose of vancomycin will be restricted to 500 mg every 8 hours.
Anaesthetics:
It has been reported that the incidence of possible adverse drug reactions (e.g. hypotension, skin flushing, erythema, urticaria, myocardial depression or pruritus) increases when vancomycin is administered concurrently with anaesthetics. To prevent these adverse drug reactions, vancomycin should be administered at least 60 minutes before anaesthetic induction.
Muscle relaxants:
If vancomycin hydrochloride is administered during or immediately after surgery, the effects of the muscle relaxants administered concurrently (in particular succinylcholine), such as neuromuscular blockade may be enhanced or prolonged.
Oral anticoagulants:
Concomitant administration of vancomycin and warfarin may increase the effects of the anticoagulants. Numerous cases of increased oral anticoagulants activity have been reported in patients receiving antibiotics. A marked infectious or inflammatory context, age and general condition of the patient appear to be risk factors. Under these circumstances, it is difficult to distinguish between the infectious disease and its treatment in the onset of the INR imbalance. It is recommended to monitor INR frequently during and rapidly after concomitant administration of vancomycin with oral anticoagulants.
Special problems of INR imbalance:
Numerous cases of increase in the activity of oral anticoagulants have been reported in patients treated with antibiotics. A marked infectious or inflammatory context, the age and the patient’s general condition appear as risk factors. Under these circumstances, it would seem difficult to differentiate between the infectious pathology and its treatment in the appearance of the INR imbalance. However, certain antibiotic classes are more deeply involved: particularly fluoroquinolones, macrolides, cyclins, cotrimoxazole and some cephalosporins.

Pregnancy:
The high therapeutic benefit of this molecule justifies that its use may be envisaged, if necessary, during pregnancy, irrespective of the term. Animal data have not demonstrated any teratogenic effect, however the clinical data remain insufficient. In view of the ototoxicity of vancomycin, an evaluation of the auditory function (oto emissions) of the newborn may be performed in case of use during pregnancy.
Lactation:
In view of the very low excretion of vancomycin in milk and its low digestive absorption, the use of vancomycin administered by injection or by oral route could be considered during breast-feeding, if necessary.

In case of overdose, the symptoms include ototoxicity, “red man’s syndrome”, and renal failure with elevation of serum creatinine and urea concentrations.
Measures to be applied in case of overdose
• There is no known specific antidote.
• Symptomatic treatment must be initiated while maintaining renal function.
Vancomycin is poorly removed from the blood by haemodialysis or peritoneal dialysis. Haemofiltration or haemoperfusion with polysulfone resins have been used to reduce serum concentrations of vancomycin.

Protect from light.
Before reconstitution: do not store above 25 °C.
After reconstitution: store between 2 °C and 8 ºC (in the fridge).