Intravenous administration  Vancomycin is indicated in all age groups for the treatment of the following infections (see sections 4.2, 4.4 and 5.1):

-  complicated skin and soft tissue infections (cSSTI)

-  bone and joint infections

-  community acquired pneumonia (CAP)

-  hospital acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP)

-  infective endocarditis

-  acute bacterial meningitis

-  bacteremia that occurs in association with, or is suspected to be associated with, any of the above.

Vancomycin is also indicated in all age groups for the perioperative antibacterial prophylaxis in patients that are at high risk of developing bacterial endocarditis when undergoing major surgical procedures.

Oral administration 

Vancomycin is indicated in all age groups for the treatment of Clostridium difficile infection (CDI) (see sections 4.2, 4.4 and 5.1).

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

Posology

Where appropriate, vancomycin should be administered in combination with other antibacterial agents.

Intravenous administration 

The initial dose should be based on total body weight. Subsequent dose adjustments should be based on serum concentrations to achieve targeted therapeutic concentrations. Renal function must be taken into consideration for subsequent doses and interval of administration.

Patients aged 12 years and older 

The recommended dose is 15 to 20 mg/kg of body weight every 8 to 12 h (not to exceed 2 g per dose). In seriously ill patients, a loading dose of 25–30 mg/kg of body weight can be used to facilitate rapid attainment of target trough serum vancomycin concentration.

Infants and children aged from one month to less than 12 years of age: 

The recommended dose is 10 to 15 mg/kg body weight every 6 hours (see section 4.4).

Term neonates (from birth to 27 days of post-natal age) and preterm neonates (from birth to the expected date of delivery plus 27 days) 

For establishing the dosing regimen for neonates, the advice of a physician experienced in the management of neonates should be sought. One possible way of dosing vancomycin in neonates is illustrated in the following table: (see section 4.4)

PMA: post-menstrual age [(time elapsed between the first day of the last menstrual period and birth (gestational age) plus the time elapsed after birth (post-natal age)]. Peri-operative prophylaxis of bacterial endocarditis in all age groups 

The recommended dose is an initial dose of 15 mg/kg prior to induction of anesthesia. Depending on the duration of surgery, a second vancomycin dose may be required.

Duration of treatment 

Suggested treatment duration is shown in table below. In any case, the duration of treatment should be tailored to the type and severity of infection and the individual clinical response.

*Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours

**Longer courses of oral suppression treatment should be considered for prosthetic joint infections

***Duration and need for combination therapy is based on valve-type and organism.

Special populations  Elderly 

Lower maintenance doses may be required due to the age-related reduction in renal function.

Renal impairment 

In adult and paediatric patients with renal impairment, consideration should be given to an initial starting dose followed by serum vancomycin trough levels rather than to a scheduled dosing regimen, particularly in patients with severe renal impairment or those who undergo renal replacement therapy (RRT) due to the many varying factors that may affect vancomycin levels in them.

In patients with mild or moderate renal failure, the starting dose must not be reduced. In patients with severe renal failure, it is preferable to prolong the interval of administration rather than administer lower daily doses.

Appropriate consideration should be given to the concomitant administration of medicinal products that may reduce vancomycin clearance and/or potentiate its undesirable effects (see section 4.4).

Vancomycin is poorly dialyzable by intermittent hemodialysis. However, use of high-flux membranes and continuous renal replacement therapy (CRRT) increases vancomycin clearance and generally requires replacement dosing (usually after the haemodialysis session in case of intermittent haemodialysis).

Adults 

Dose adjustments in adult patients could be based on glomerular filtration rate estimated (eGFR) by the following formula:

Men: [Weight (kg) x 140 - age (years)]/ 72 x serum creatinine (mg/dl) Women: 0.85 x value calculated by the above formula.

The usual starting dose for adult patients is 15 to 20 mg/kg that could be administered every 24 hours in patients with creatinine clearance between 20 to 49 ml/min. In patients with severe renal impairment (creatinine clearance below 20 ml/min) or those on renal replacement therapy, the appropriate timing and amount of subsequent doses largely depend on the modality of RRT and should be based on serum vancomycin trough levels and on residual renal function (see section 4.4). Depending on the clinical situation, consideration could be given to withhold the next dose while awaiting the results of vancomycin levels.

In the critically ill patient with renal insufficiency, the initial loading dose (25 to 30 mg/kg) should not be reduced. Paediatric population 

Dose adjustments in paediatric patients aged 1 year and older could be based on glomerular filtration rate estimated (eGFR) by the revised Schwartz formula:

eGFR (mL/min/1.73m² ) = (height cm x 0.413)/ serum creatinine (mg/dl) eGFR (mL/min/1.73m²)= (height cm x 36.2/serum creatinine (μmol/L)

For neonates and infants below 1 year of age, expert advice should be sought as the revised Schwartz formula is not applicable to them.

Orientative dosing recommendations for the paediatric population are shown in table below that follow the same principles as in adult patients.

*The appropriate timing and amount of subsequent doses largely depends on the modality of RRT and should be based on serum vancomycin levels obtained prior to dosing and on residual renal function. Depending on the clinical situation, consideration could be given to withhold the next dose while awaiting the results of vancomycin levels.

Hepatic impairment:  

No dose adjustment is needed in patients with hepatic insufficiency.

Pregnancy 

Significantly increased doses may be required to achieve therapeutic serum concentrations in pregnant women (see Section 4.6).

Obese patients  

In obese patients, the initial dose should be individually adapted according to total body weight as in non-obese patients.

Therapeutic trough (minimum) vancomycin blood levels should normally be 10-20 mg/l, depending on the site of infection and susceptibility of the pathogen. Trough values of 15-20 mg/l are usually recommended by clinical laboratories to better cover susceptible pathogens with

MIC ≥1 mg/L (see sections 4.4 and 5.1).

Model-based methods may be useful in the prediction of individual dose requirements to reach an adequate AUC. The model-based approach can be used both in calculating the personalized starting dose and for dose adjustments based on TDM results (see section 5.1).

Method of administration 

Intravenous administration : Intravenous vancomycin is usually administered as an intermittent infusion and the dosing recommendations presented in this section for the intravenous route correspond to this type of administration.

Vancomycin shall only be administered as slow intravenous infusion of at least one hour duration or at a maximum rate of 10 mg/min (whichever is longer) which is sufficiently diluted (at least 100 ml per 500 mg or at least 200 ml per 1000 mg) (see section 4.4).

Patients whose fluid intake must be limited can also receive a solution of 500 mg/50 ml or 1000 mg/100 ml, although the risk of infusion-related undesirable effects can be increased with these higher concentrations.

For information about the preparation of the solution, please see section 6.6.

Continuous vancomycin infusion may be considered, e.g., in patients with unstable vancomycin clearance.

Information on reconstitution and dilution of the medicinal product before use, see section 6.6.

Hypersensitivity reactions 

Serious and occasionally fatal hypersensitivity reactions are possible (see sections 4.3 and 4.8). 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 hematologic 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 (see section 4.8) 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 (i.e. over several minutes) may be associated with exaggerated hypotension (including shock and, rarely, cardiac arrest), histamine like responses and maculopapular or erythematous rash (“red man's syndrome” or “red neck syndrome”). Vancomycin should be infused slowly in a dilute solution (2.5 to 5.0 mg/ml) at a rate no greater than 10 mg/min and over a period 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 (hypotension, flushing, erythema, urticaria and pruritus) increases with the concomitant administration of anaesthetic agents (see section 4.5). This may be reduced by administering vancomycin by infusion over at least 60 minutes, before anaesthetic induction.

Severe bullous reactions 

Stevens-Johnson syndrome (SJS) has been reported with the use of vancomycin (see section 4.8). If symptoms or signs of SJS (e.g. progressive skin rash often with blisters or mucosal lesions) are present, vancomycin treatment should be discontinued immediately and specialised dermatological assessment be sought. 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 (see section 4.2) 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.

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 (see section 4.2).

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. 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 (see section 4.5) 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 (see section 4.2).

Drug interactions with anesthetic 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 (see section 4.5).

Pseudomembranous enterocolitis 

In case of severe persistent diarrhoea the possibility of pseudomembranous enterocolitis that might be life-threatening has to be taken into account (see section 4.8). Anti-diarrhoeic medicinal products must not be given. Superinfection 

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.

Oral administration 

Intravenous administration of vancomycin is not effective for the treatment of Clostridium difficile infection. Vancomycin should be administered orally for this indication.

Testing for Clostridium difficile colonization or toxin is not recommended in children younger than 1 year due to high rate of asymptomatic colonisation unless severe diarrhoea is present in infants with risk factors for stasis such as Hirschsprung disease, operated anal atresia or other severe motility disorders. Alternative aetiologies should always be sought and Clostridium difficile enterocolitis be proven.

Potential for Systemic Absorption 

Absorption may be enhanced in patients with inflammatory disorders of the intestinal mucosa or with Clostridium difficile-induced pseudomembranous colitis. These patients may be at risk for the development of adverse reactions, especially if there is a concomitant renal impairment. The greater the renal impairment, the greater the risk of developing the adverse reactions associated with the parenteral administration of vancomycin. Monitoring of serum vancomycin concentrations of patients with inflammatory disorders of the intestinal mucosa should be performed.

Nephrotoxicity 

Serial monitoring of renal function should be performed when treating patients with underlying renal dysfunction or patients receiving concomitant therapy with an aminoglycoside or other nephrotoxic drugs.

Ototoxicity 

Serial tests of auditory function may be helpful in order to minimise the risk of ototoxicity in patients with an underlying hearing loss, or who are receiving concomitant therapy with an ototoxic agent such as an aminoglycoside.

Drug interactions with anti-motility agents and proton pump inhibitors  

Anti-motility agents should be avoided and proton pump inhibitor use should be reconsidered.

Development of Drug-Resistant Bacteria 

Oral vancomycin use increases the chance of vancomycin-resistant Enterococci populations in the gastrointestinal tract. As a consequence, prudent use of oral vancomycin is advised.

Concurrent administration of vancomycin and anaesthetic agents has been associated with erythema, histamine like flushing and anaphylactoid reactions.

Concurrent administration with other neurotoxic or nephrotoxic drugs, e.g. amphotericin B, streptomycin, neomycin, gentamicin, kanamycin, amikacin, tobramycin, bacitracin, polymyxin B, colistin and cisplatin requires careful monitoring.

Diuretics such as ethacrynic acid and frusemide may aggravate ototoxicity.

Cholestyramine has been shown to bind vancomycin in-vitro. Therefore, if oral Vancomycin is used with cholestyramine, the two drugs should be administered several hours apart. 

Use 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. Vancomycin should be given in pregnancy only if clearly needed and blood levels should be monitored carefully to minimise the risk of foetal toxicity. It has been reported, however, that pregnant patients may require significantly increased doses of vancomycin to achieve therapeutic serum concentrations.

Use in Lactation:  

Vancomycin Hydrochloride is excreted in breast milk but it is not known whether it is harmful to the newborn. Therefore, it is not recommended for nursing mothers unless the expected benefits outweigh any potential risk.

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Summary of the Safety profile 

The most common adverse reactions are phlebitis, pseudo-allergic reactions and flushing of the upper body (“red-neck syndrome”) in connection with too rapid intravenous infusion of vancomycin.

The absorption of vancomycin from the gastrointestinal tract is negligible. However, in severe inflammation of the intestinal mucosa, especially in combination with renal insufficiency, adverse reactions that occur when vancomycin is administered parenterally may appear.

Tabulated List of Adverse reactions 

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

The adverse reactions listed below are defined using the following MedDRA convention and system organ class database: Very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon

(≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Description of selected adverse drug reactions 

Reversible neutropenia usually starting one week or more after onset of intravenous therapy or after total dose of more than 25 g.

During or shortly after rapid infusion anaphylactic/anaphylactoid reactions including wheezing may occur. The reactions abate when administration is stopped, generally between 20 minutes and 2 hours. Vancomycin should be infused slowly (see sections 4.2 and 4.4). Necrosis may occur after intramuscular injection.

Tinnitus, possibly preceding onset of deafness, should be regarded as an indication to discontinue treatment.

Ototoxicity has primarily been reported in patients given high doses, or in those on concomitant treatment with other ototoxic medicinal product like aminoglycoside, or in those who had a preexisting reduction in kidney function or hearing.

If a bullous disorder is suspected, the drug should be discontinued and specialised dermatological assessment should be carried out.

Paediatric population 

The safety profile is generally consistent among children and adult patients. Nephrotoxicity has been described in children, usually in association with other nephrotoxic agents such as aminoglycosides.

Reporting of suspected adverse reactions 

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects    not listed in this leaflet. You can also report side effects directly (see details below). By reporting side affects; you can help provide more information on the safety of this medicine.

• Saudi Arabia:

Other GCC States:
Please contact the relevant competent authority.

Supportive care is advised, with maintenance of glomerular filtration. Vancomycin is poorly removed from the blood by haemodialysis or peritoneal dialysis. Haemoperfusion with Amberlite resin XAD-4 has been reported to be of limited benefit.

Pharmacotherapeutic group: Anti-infective for systemic use 

Therapeutic subgroup: Antibacterial for systemic use

Pharmacological subgroup: Other antibacterial

Chemical subgroup: Glycopeptide antibacterial

ATC Code: J01X01

Mechanism of action 

Vancomycin is a tricyclic glycopeptide antibiotic that inhibits the synthesis of the cell wall in sensitive bacteria by binding with high affinity to the D-alanyl-D-alanine terminus of cell wall precursor units. The drug is slowly bactericidal for dividing microorganisms. In addition, it impairs the permeability of the bacterial cell membrane and RNA synthesis.

Pharmacokinetic/ Pharmacodynamic relationship 

Vancomycin displays concentration-independent activity with the area under the concentration curve (AUC) divided by the minimum inhibitory concentration (MIC) of the target organism as the primary predictive parameter for efficacy. On basis of in vitro, animal and limited human data, an AUC/MIC ratio of 400 has been established as a PK/PD target to achieve clinical effectiveness with vancomycin. To achieve this target when MICs are ≥ 1.0 mg/l, dosing in the upper range and high trough serum concentrations (15-20 mg/l) are required (see section 4.2).

Mechanism of resistance 

Acquired resistance to glycopeptides is most common in enterococci and is based on acquisition of various van gene complexes which modifies the D-alanyl-D-alanine target to D-alanyl-Dlactate or D-alanyl-D-serine which bind vancomycin poorly. In some countries, increasing cases of resistance are observed particularly in enterococci; multi-resistant strains of Enterococcus faecium are especially alarming.

Van genes have rarely been found in Staphylococcus aureus, where changes in cell wall structure result in “intermediate” susceptibility, which is most commonly heterogeneous. Also, methicillin-resistant staphylococcus strains (MRSA) with reduced susceptibility for vancomycin were reported. The reduced susceptibility or resistance to vancomycin in Staphylococcus is not well understood. Several genetic elements and multiple mutations are required.

There is no cross-resistance between vancomycin and other classes of antibiotics. Crossresistance with other glycopeptide antibiotics, such as teicoplanin, does occur. Secondary development of resistance during therapy is rare.

Synergism 

The combination of vancomycin with an aminoglycoside antibiotic has a synergistic effect against many strains of Staphylococcus aureus, non-enterococcal group D-streptococci, enterococci and streptococci of the Viridans group. The combination of vancomycin with a cephalosporin has a synergistic effect against some oxacillin-resistant Staphylococcus epidermidis strains, and the combination of vancomycin with rifampicin has a synergistic effect against Staphylococcus epidermidis and a partial synergistic effect against some Staphylococcus aureus strains. As vancomycin in combination with a cephalosporin may also have an antagonistic effect against some Staphylococcus epidermidis strains and in combination with rifampicin against some Staphylococcus aureus strains, preceding synergism testing is useful.

Specimens for bacterial cultures should be obtained in order to isolate and identify the causative organisms and to determine their susceptibility to vancomycin.

Susceptibility testing breakpoints 

Vancomycin is active against gram-positive bacteria, such as staphylococci, streptococci, enterococci, pneumococci, and clostridia. Gram-negative bacteria are resistant.

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. This information only provides approximate guidance on the chance whether micro-organisms are susceptible to vancomycin.

Minimum inhibitory concentration (MIC) breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) are as follows:

¹ S. aureus with vancomycin MIC values of 2 mg/L are on the border of the wild type distribution and there may be an impaired clinical response.

Absorption 

Vancomycin is administered intravenously for the treatment of systemic infections. 

In the case of patients with normal renal function, intravenous infusion of multiple doses of 1g vancomycin (15 mg/kg) for 60 minutes produces approximate average plasma concentrations of 50-60 mg/L, 20-25 mg/L and 5-10 mg/L, immediately, 2 hours and 11 hours after completing the infusion, respectively. The plasma levels obtained after multiple doses are similar to those achieved after a single dose.

Vancomycin is not usually absorbed into the blood after oral administration. However, absorption may occur after oral administration in patients with (pseudomembranous) colitis. This may lead to vancomycin accumulation in patients with co-existing renal impairment.

Distribution 

The volume of distribution is about 60 L/1.73 m² body surface. At serum concentrations of vancomycin of 10 mg/l to 100 mg/l, the binding of the drug to plasma proteins is approximately 30-55%, measured by ultra-filtration.

Vancomycin diffuses readily across the placenta and is distributed into cord blood. In noninflamed meninges, vancomycin passes the blood-brain barrier only to a low extent.

Biotransformation 

There is very little metabolism of the drug. After parenteral administration it is excreted almost completely as microbiologically active substance (approx. 75-90% within 24 hours) through glomerular filtration via the kidneys.

Elimination 

The elimination half-life of vancomycin is 4 to 6 hours in patients with normal renal function and

2.2-3 hours in children. Plasma clearance is about 0.058 L/kg/h and kidney clearance about 0.048 L/kg/h. In the first 24 hours, approximately 80 % of an administered dose of vancomycin is excreted in the urine through glomerular filtration. Renal dysfunction delays the excretion of vancomycin. In anephric patients, the mean half-life is 7.5 days. Due to ototoxicity of vancomycin therapy-adjuvant monitoring of the plasma concentrations is indicated in such cases. Biliary excretion is insignificant (less than 5% of a dose).

Although the vancomycin is not eliminated efficiently by haemodialysis or peritoneal dialysis, there have been reports of an increase in vancomycin clearance with haemoperfusion and haemofiltration.

After oral administration, only a fraction of the administered dose is recovered in the urine. In contrast, high concentrations of vancomycin are found in the faeces (>3100 mg/kg with doses of 2 g/day).

Linerarity/non-linearity 

Vancomycin concentration generally increases proportionally with increasing dose. Plasma concentrations during multiple dose administration are similar to those after the administration of a single dose.

Characteristics in specific groups 

Renal impairment 

Vancomycin is primarily cleared by glomerular filtration. In patients with impaired renal function the terminal elimination half- life of vancomycin is prolonged and the total body clearance is reduced. Subsequently, optimal dose should be calculated in line with dosing recommendations provided in section 4.2. Hepatic impairment 

Vancomycin pharmacokinetics is not altered in patients with hepatic impairment.

Pregnant Women: 

Significantly increased doses may be required to achieve therapeutic serum concentrations in pregnant women (see Section 4.6). Overweight patients 

Vancomycin distribution may be altered in overweight patients due to increases in volume of distribution, in renal clearance and possible changes in plasma protein binding. In these subpopulations vancomycin serum concentration were found higher than expected in male healthy adults (see section 4.2).

Paediatric population 

Vancomycin PK has shown wide inter-individual variability in preterm and term neonates. In neonates, after intravenous administration, vancomycin volume of distribution varies between 0.38 and 0.97 L/kg, similar to adult values, while clearance varies between 0.63 and 1.4 ml/kg/min. Half-life varies between 3.5 and 10 h and is longer than in adults, reflecting the usual lower values for clearance in the neonate.

In infants and older children, the volume of distribution ranges between 0.26-1.05 L/kg while clearance varies between 0.33-1.87 ml/kg/min.

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The other ingredients are: Sodium hydroxide, Hydrochloric acid, Water for Injection

Vancomycin solution has a low pH that may cause chemical or physical instability when it is mixed with other compounds.

Chemically incompatible with dexamethasone sodium phosphate, Heparin sodium, methicillin sodium, phenobarbitone sodium, sodium bicarbonate.

Store below 30°C. Keep container in the outer carton.

500 mg: Clear Type I glass vial with rubber stopper in packs of 1 vial

For single use. Discard any unused contents.

Reconstitute Details: 

Primary Diluent – Sterile water for Injection

Secondary Diluent - 5% Dextrose and 0.9% Sodium Chloride Injection 

                                  5% Dextrose and Lactated Ringer's Injection 

Preparation and Stability:

At the time of use reconstitute the vials of Vancomycin Hydrochloride for Injection USP with Sterile Water for Injection to a concentration of 50mg /mL of Vancomycin / mL.

For 500mg Vial : 10mL of Diluent ( Sterile Water For Injection) to be used

For 1000mg Vial : 20mL of Diluent ( Sterile Water For Injection ) to be used

After dilution store below 30°C not more than 24 hours. Or in refrigerator 2 - 8 °C for not more than 36 hours.

Reconstituted solutions of Vancomycin (500mg/10mL) must be further diluted with at least 100mL of a suitable infusion solution.

Reconstituted solutions of Vancomycin (1000mg/20mL) must be further diluted with at least 200mL of a suitable infusion solution.

The desired dose, diluted in this manner, should be administered by intermittent IV Infusion over a period of at least 60 minutes.

Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration, whenever solution and container permit.