Vancomycin A.P.

Package leaflet: Information for the patient

Vancocina A.P.

500 mg, powder for concentrate for solution for infusion and for oral solution
vancomycin
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What Vancocina A.P. is and what it is used for
2. What you need to know before using Vancocina A.P.
3. How to use Vancocina A.P.
4. Possible side effects
5. How to store Vancocina A.P.
6. Contents of the pack and other information

1. What Vancocina A.P. is and what it is used for

Vancomycin is an antibiotic belonging to a class of antibiotics known as "glycopeptides".
Vancomycin A.P. works by eliminating certain bacteria that cause infections.
Vancomycin powder is reconstituted to form a solution for infusion or oral solution.
Vancocina A.P. is used in all age groups by infusion for the treatment of the following serious infections:

• Infections of the skin and underlying tissue.
• Infections of bones and joints.
• Lung infection known as "pneumonia".
• Infection of the inner lining of the heart (endocarditis), and for prevention of endocarditis in at-risk patients undergoing major surgical procedures.
• Infection of the central nervous system.
• Blood infection associated with the above-mentioned infections.

Vancocina A.P. is used in adults and children for the treatment of mucosal infections of the small and large intestine with mucosal damage (pseudomembranous colitis), caused by the bacterium Clostridium difficile.

2. What you need to know before using Vancocina A.P.

Do not use Vancocina A.P.

• If you are allergic to vancomycin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, hospital pharmacist, or nurse before using Vancocina A.P. if:

• You have previously had an allergic reaction to the medicine teicoplanin, as this may mean you are also allergic to Vancocina A.P.
• You have a hearing disorder, especially if you are elderly (you may require hearing tests during treatment).
• You have kidney disease (you will need blood and kidney tests during treatment).
• You are receiving Vancocina A.P. by infusion for the treatment of Clostridium difficile-associated diarrhoea rather than orally.
• You have ever developed a severe skin rash, skin peeling, blisters, and/or mouth ulcers after taking vancomycin.

Serious skin reactions have been reported in association with vancomycin treatment, including
Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and
systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). Discontinue
vancomycin and seek immediate medical attention if you experience any of the symptoms described in
section 4.
Talk to your doctor, hospital pharmacist, or nurse during treatment with
Vancocina A.P. if:

• You have been treated with Vancocina A.P. for a prolonged period (you may require blood, liver, and kidney tests during treatment).
• You develop any skin reaction during treatment.
• You develop severe and persistent diarrhoea during or after taking Vancocina A.P., contact your doctor immediately. This may be a sign of inflammation of the intestine (pseudomembranous colitis), which can occur following antibiotic treatment.

Serious adverse effects leading to vision loss have been reported following injection of vancomycin into
the eyes.
Signs of allergic reaction to this medicine, including breathing difficulties and chest pain, have been
reported with Vancocina A.P. Discontinue Vancocina A.P. immediately and contact your doctor or
emergency medical services immediately if you notice any of these signs.
Children
Vancocina A.P. will be used with particular caution in premature infants and newborns, as their kidneys are not fully developed and may accumulate vancomycin in the blood. This age group requires blood tests to monitor vancomycin blood levels.
Concomitant administration of Vancocina A.P. and anaesthetic agents has been associated with skin
flushing (erythema) and allergic reactions in children. Similarly, concomitant use with other medicines such as aminoglycoside antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs, e.g. ibuprofen), or amphotericin B (a medicine for fungal infections) may increase the risk of kidney damage, and therefore more frequent blood and kidney tests may be required.
Elderly
If you are elderly, your doctor will adjust the dose of Vancocina A.P.
Other medicines and Vancocina A.P.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Particular caution is required if you are taking/using other medicines, as some may interact with vancomycin, for example:

• Other medicines with potential toxicity to the hearing and kidneys, such as aminoglycosides, amphotericin B, bacitracin, cisplatin, colistin, polymyxin B, piperacillin/tazobactam, especially in patients with pre-existing hearing loss or reduced kidney function;
• Anaesthetics, as skin reactions (cutaneous erythema and flushing) and severe, sudden allergic reactions (anaphylactoid reactions) may occur;
• Medicines that block muscles and their nerves (neuromuscular blockers), as the blocking effect may be increased.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
Pregnancy
There is insufficient experience regarding the safety of Vancocina A.P. taken during pregnancy.
Vancocina A.P. crosses the placenta, and a potential risk of toxic effects on the embryo’s and newborns’ hearing and kidneys cannot be excluded. Therefore, if you are pregnant, Vancocina A.P. should be used only if necessary and only after careful assessment of the risk/benefit ratio by your doctor.
Breastfeeding
Vancocina A.P. is also excreted in breast milk. If you are breastfeeding, your doctor will exercise caution due to the potential adverse effects of the medicine in the breastfed infant (gastrointestinal disturbances with diarrhoea, fungal infections, and possible allergic reactions).
If treatment with Vancocina A.P. is necessary, your doctor should consider the possibility of advising you to stop breastfeeding.
Driving and using machines
No adverse effects on the ability to drive or operate machinery are known.

3. How to use Vancocina A.P.

Vancocina A.P. will be administered to you by medical staff while you are in hospital. Your doctor will decide how much of this medicine you should receive each day and how long your treatment will last.
Dosage
The dose administered will depend on:

• your age,
• your body weight,
• the type of infection you have,
• your kidney function,
• your hearing ability,
• other medicines you are taking.

Intravenous administration
Adults and adolescents (from 12 years of age)
The dose will be calculated based on your body weight. The usual infusion dose is 15–20 mg per kg of body weight. It is generally administered every 8–12 hours. In some cases, your doctor may decide to administer an initial dose of up to 30 mg per kg of body weight. The maximum dose must not exceed 2 g per dose.
Use in children
Children from 1 month up to less than 12 years of age
The dose will be calculated based on body weight. The usual infusion dose is 10–15 mg per kg of body weight. It is generally administered every 6 hours.
Premature and full-term neonates (from 0 to 27 days of age)
Dosage will be calculated based on post-menstrual age [(time elapsed from the first day of the last menstrual period to birth (gestational age) plus time elapsed after birth (postnatal age))].
Elderly patients, pregnant women, and patients with renal disease, including those on dialysis, may require a different dose.
Oral administration
For adults and adolescents (from 12 to 18 years of age)
The recommended dose is 125 mg every 6 hours. In some cases, your doctor may decide to give you a higher daily dose, up to 500 mg every 6 hours. The maximum daily dose must not exceed 2 g.
If you have previously experienced further episodes (mucosal infection), you may require a different dose and duration of therapy.
Use in children
Neonates, infants and children under 12 years of age
The recommended dose is 10 mg per kg of body weight. It is generally administered every 6 hours. The maximum daily dose must not exceed 2 g.
Method of administration
Intravenous infusion means that the medicine flows from an infusion bottle or bag through a tube into one of your blood vessels and into the body. The doctor or nurse will always administer vancomycin into your bloodstream and never into muscle.
Vancomycin will be administered intravenously over at least 60 minutes.
If administered for gastrointestinal disorders (so-called pseudomembranous colitis), the medicine must be given as an oral solution (you will take the medicine by mouth).
Duration of treatment
The duration of treatment depends on the infection you have and may last several weeks.
The duration of therapy may vary for each patient depending on individual response to treatment.
During treatment, you may need to undergo blood tests; you may also be asked to provide urine samples and undergo hearing tests to monitor for possible adverse effects.
If you use more Vancocina A.P. than you should
This medicine will be administered to you by medical staff while you are in hospital.
It is unlikely that you will receive more than you should. Your doctor will monitor the amount of Vancocina A.P. you are given.
In case of accidental ingestion/overdose of Vancocina A.P., inform your doctor immediately.
If you stop treatment with Vancocina A.P.
If you have any doubts about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Stop using vancomycin and consult a doctor immediately if you notice any of the following
symptoms:

• Red, flat, target-shaped or circular spots on the trunk, often with central blisters, skin peeling, mouth ulcers, and ulcers of the throat, nose, genitals, and eyes. These serious skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome and toxic epidermal necrolysis).
• Widespread rash, high body temperature, and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
• Widespread, red, scaly rash with subcutaneous bumps and blisters accompanied by fever at the beginning of treatment (acute generalized exanthematous pustulosis).
• Chest pain, which may be a sign of a potentially serious allergic reaction known as Kounis syndrome.

Vancomycin A.P. may cause allergic reactions, although severe allergic reactions (anaphylactic shock) are rare. Inform your doctor immediately if you experience sudden wheezing, difficulty breathing, redness of the upper body, rash, or itching.
Vancomycin absorption from the gastrointestinal tract is negligible. However, if you have an inflammatory disease of the digestive tract, especially if you also have kidney disease, side effects may occur that are typically seen when vancomycin is administered by infusion.

Common side effects (may affect up to 1 in 10 people):

• Decrease in blood pressure
• Shortness of breath, noisy breathing (a high-pitched sound caused by obstruction of airflow in the upper airways)
• Mouth inflammation and rash, itching, itchy rash, hives
• Kidney problems, which may mainly be detected through blood tests
• Redness of the upper body and face, inflammation of a vein
• Increased liver enzymes

Uncommon side effects (may affect up to 1 in 100 people):

• Temporary or permanent hearing loss

Rare side effects (may affect up to 1 in 1,000 people):

• Decrease in white blood cells, red blood cells, and platelets (blood cells responsible for clotting)
• Increase in certain white blood cells in the blood
• Loss of balance, ringing in the ears, dizziness
• Inflammation of blood vessels
• Nausea (feeling of disgust)
• Kidney inflammation and kidney failure
• Chest and back muscle pain
• Fever, chills

Very rare side effects (may affect up to 1 in 10,000 people):

• Sudden onset of a severe allergic reaction with blistering or skin peeling. This may be associated with high fever and joint pain
• Cardiac arrest
• Intestinal inflammation causing abdominal pain and diarrhoea, which may contain blood

Frequency not known (frequency cannot be estimated from the available data):

• Vomiting, diarrhoea
• Confusion, dizziness, loss of energy, swelling, fluid retention, reduced urine output
• Rash with swelling or pain behind the ears, neck, groin, under the chin, and armpits (swollen lymph nodes), abnormal liver function and blood test results
• Rash with blisters and fever
• Excessive breakdown of red blood cells leading to fatigue and pale skin (haemolytic anaemia)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, hospital pharmacist, or nurse. You can also report side effects directly via the national reporting system at
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Vancocina A.P.

Keep this medicine out of sight and reach of children.
Store at a temperature not exceeding 25°C.
After dilution, the solution can be stored in the refrigerator (between +2 and +8°C).
Vancocina A.P. is stable for 14 days in the refrigerator after initial reconstitution. Any further
dilution is stable for 24 hours at room temperature.
For further information on storage conditions, see the section intended exclusively for
healthcare professionals.
Do not use this medicine after the expiry date stated on the carton after the abbreviation
“Exp.”. The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Vancocina A.P. Contains
Vancocina A.P. 500 mg powder for concentrate for infusion solution and for oral solution
The active substance is:
500 mg vancomycin hydrochloride equivalent to 500,000 IU of vancomycin.
The other component is: mannitol (E421).

Description of the Appearance of Vancocina A.P. and Contents of the Pack
Powder for concentrate for infusion solution and for oral solution, 1 vial.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
VANCOCIN ITALIA S.R.L., Via Ferreri 11 – 27100 Pavia (PV)
Manufacturer
Vianex S.A. (Plant C), Marathonos Avenue 16th KM Pallini, Attiki – 153 51 Greece

Additional Sources of Information
Medical Advice/Information
Antibiotics are used to treat bacterial infections. They are ineffective against viral infections. If your doctor has prescribed antibiotics, they are specifically intended for your current illness.
Despite antibiotic treatment, some bacteria may survive or grow. This phenomenon is known as resistance: certain antibiotic treatments may become ineffective.
Antibiotic abuse increases resistance. It may also help bacteria become resistant, thereby delaying treatment or reducing antibiotic effectiveness if the appropriate:

• dosage
• regimen
• duration of treatment

is not followed.
Therefore, to maintain the effectiveness of this medicine:
1 – Use antibiotics only when prescribed.
2 – Follow instructions strictly.
3 – Do not reuse an antibiotic without a medical prescription, even if you wish to treat a similar illness.

The following information is intended exclusively for physicians or healthcare professionals.

What Vancocina A.P. Is Used For
Intravenous Administration
Vancocina A.P. is indicated in all age groups for the treatment of the following infections:

• 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 occurring in association with, or suspected to be associated with, any of the infections listed above. Vancocina A.P. is also indicated in all age groups for perioperative antibacterial prophylaxis in patients at high risk of developing bacterial endocarditis undergoing major surgical procedures.

Oral Administration
Vancomycin is indicated in all age groups for the treatment of Clostridium difficile infection (CDI).
Reference should be made to official guidelines on the appropriate use of antibacterial agents.

Warnings and Precautions
Hypersensitivity Reactions
Serious, and occasionally fatal, hypersensitivity reactions may occur. In the event of hypersensitivity reactions, vancomycin treatment must be discontinued immediately and appropriate emergency measures initiated.
In patients receiving vancomycin for prolonged periods or in combination with other medicinal products that may cause neutropenia or agranulocytosis, white blood cell counts should be monitored at regular intervals. All patients receiving vancomycin should undergo periodic hematological examinations, urine analysis, 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.

Antibacterial Spectrum of Activity
Vancomycin has a limited antibacterial spectrum restricted to Gram-positive organisms. It is not indicated as monotherapy for certain types of infections unless the causative pathogen has been documented and is known to be susceptible, or there is strong suspicion that the most likely pathogens are sensitive to vancomycin treatment.
The rational use of vancomycin should take into account its antibacterial spectrum, safety profile, and adequacy of standard antibacterial therapy for the individual patient.

Ototoxicity
Ototoxicity, which may be transient or permanent, has been reported in patients with pre-existing hearing loss, those receiving excessive intravenous doses, or those undergoing concomitant treatment with another ototoxic substance such as an aminoglycoside. Vancomycin should also be avoided in patients with pre-existing hearing loss. Tinnitus may precede deafness. Experience with other antibiotics suggests that hearing loss may progress despite discontinuation of treatment. To reduce the risk of ototoxicity, blood levels should be periodically monitored, and periodic auditory function tests are recommended.
Elderly patients are particularly sensitive to hearing damage. Monitoring of vestibular and auditory function should be performed during and after treatment in elderly patients. Concomitant 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 syndrome" or "red neck syndrome"). Vancomycin must be administered slowly in a diluted solution (2.5–5.0 mg/mL) at a rate not exceeding 10 mg/min and over a period of no less than 60 minutes to avoid rapid infusion-related reactions.
Discontinuation of the infusion generally leads to abrupt cessation of these reactions.
The frequency of infusion-related reactions (hypotension, flushing, erythema, urticaria, and pruritus) increases with concomitant administration of anesthetic agents. This can be reduced by administering vancomycin via infusion over at least 60 minutes prior to anesthesia induction.

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 generalized 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 up to eight weeks after initiation of vancomycin therapy.
At the time of prescription, patients must be informed of the signs and symptoms and closely monitored for skin reactions. If signs or symptoms suggestive of these reactions occur, vancomycin must be discontinued immediately and alternative treatment considered.
If a patient has developed a SCAR during vancomycin use, vancomycin treatment must not be resumed at any time.

Administration Site-Related Reactions
Pain and thrombophlebitis, occasionally severe, may occur in many patients receiving intravenous vancomycin. The frequency and severity of thrombophlebitis can be minimized by slow administration of the product as a diluted solution and by regularly changing infusion sites.
The efficacy and safety of vancomycin have not been established for intrathecal, intralumbar, or intraventricular administration routes.

Nephrotoxicity
Vancomycin should be used with caution in patients with renal impairment, including anuria, as the risk of developing toxic effects is much higher in the presence of prolonged high blood concentrations. The risk of toxicity is increased by high blood levels or prolonged therapy.
Regular monitoring of vancomycin levels is recommended during high-dose therapy and long-term use, particularly in patients with renal dysfunction or impaired hearing, as well as in cases of concomitant administration of nephrotoxic or ototoxic substances.

Eye Disorders
Vancomycin is not authorized for intracameral or intravitreal use, including endophthalmitis prophylaxis.
Occlusive retinal hemorrhagic vasculitis (HORV), including permanent vision loss, has been observed in isolated cases following intracameral or intravitreal use of vancomycin during or after cataract surgery.

Pediatric Population
Current recommendations for intravenous dosing in the pediatric population, particularly in children under 12 years of age, may result in subtherapeutic vancomycin levels in a high number of children. However, the safety of higher vancomycin dosing has not been adequately evaluated, and doses exceeding 60 mg/kg/day cannot generally be recommended.
Vancomycin should be used with particular caution in premature neonates and young children due to their renal immaturity and the potential for increased serum vancomycin concentrations. Serum vancomycin concentrations must therefore be closely monitored in these children.
Concomitant administration of vancomycin and anesthetic 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 patent ductus arteriosus closure), and amphotericin B is associated with an increased risk of nephrotoxicity, and more frequent monitoring of serum vancomycin levels and renal function is indicated.

Use in the Elderly
The natural decline in glomerular filtration rate with increasing age may lead to elevated serum vancomycin concentrations if dosage adjustments are not made.

Pharmacological Interactions with Anesthetic Agents
Myocardial depression induced by anesthetics may be enhanced by vancomycin. During anesthesia, vancomycin doses should be well diluted and administered slowly with careful cardiac monitoring. Position changes should be delayed until the infusion is complete to allow for postural adjustment.

Pseudomembranous Enterocolitis
In cases of severe and persistent diarrhea, pseudomembranous enterocolitis, which may be potentially fatal, should be considered. Antidiarrheal medications must not be administered.

Superinfection
Prolonged use of vancomycin may lead to superinfections caused by non-susceptible organisms. Close patient observation is essential. If superinfections occur during therapy, appropriate measures must be taken.

Oral Administration
Intravenous administration of vancomycin is not effective for the treatment of Clostridium difficile infection. Vancomycin must be administered orally for this indication.
Testing for Clostridium difficile colonization or toxin is not recommended in children under 1 year of age due to the high rate of asymptomatic colonization, unless severe diarrhea is present in infants with risk factors for stasis, such as Hirschsprung's disease, operated anal atresia, or other severe motility disorders. Alternative etiologies must always be investigated, and Clostridium difficile enterocolitis must be confirmed.

Potential for Systemic Absorption
Absorption may be increased in patients with inflammatory disorders of the intestinal mucosa or with Clostridium difficile-induced pseudomembranous colitis. These patients may be at risk of developing adverse reactions, especially if concomitant renal impairment is present. The greater the renal impairment, the higher the risk of developing adverse reactions associated with parenteral vancomycin administration. Monitoring of serum vancomycin concentrations is required in patients with inflammatory disorders of the intestinal mucosa.

Nephrotoxicity
Periodic monitoring of renal function should be performed when treating patients with pre-existing renal dysfunction or those receiving concomitant therapy with an aminoglycoside or other nephrotoxic drugs.

Ototoxicity
Periodic auditory function tests may be useful to minimize the risk of ototoxicity in patients with pre-existing hearing loss or those receiving concomitant therapy with an ototoxic agent such as an aminoglycoside.

Pharmacological Interactions with Anti-Motility Agents and Proton Pump Inhibitors
Anti-motility agents should be avoided, and the use of proton pump inhibitors should be re-evaluated.

Development of Drug-Resistant Bacteria
The use of oral vancomycin increases the likelihood of vancomycin-resistant Enterococci populations in the gastrointestinal tract. Consequently, prudent use of oral vancomycin is advised.

How to Use Vancocina A.P.
Dosage
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 established therapeutic levels. Renal function should be considered for subsequent doses and dosing intervals.

Patients aged 12 years and older
The recommended dose is 15–20 mg/kg body weight every 8–12 hours (should not exceed 2 g per dose).
In critically ill patients, an initial dose of 25–30 mg/kg body weight may be used to facilitate rapid achievement of the target minimum serum concentration.

Infants and children from 1 month to 12 years of age
The recommended dose is 10–15 mg/kg body weight every 6 hours.

Term neonates (from birth up to 27 days of age) and preterm neonates (from birth up to 27 days after the expected date of delivery)
To establish the dosing regimen for neonates, expert medical advice in neonatal care should be sought. A possible vancomycin dosing regimen for neonates is shown in the following table:

PMA: postmenstrual age [(time elapsed from the first day of the last menstrual period to birth (gestational age) plus the time elapsed after birth (postnatal age))].
Perioperative prophylaxis of bacterial endocarditis in all age groups
The recommended dose is an initial dose of 15 mg/kg before induction of anesthesia. Depending on the duration of the procedure, a second dose of vancomycin may be required.
Duration of treatment
The suggested duration of treatment is shown in the table below. In any case, the duration of treatment should be adjusted according to the type and severity of the infection and the individual clinical response.

*Continue until no further debridement is required, the patient has clinically improved,
and the patient has been afebrile for 48–72 hours.
**In the case of prosthetic joint infections, longer durations of oral antibiotic suppressive therapy should be considered with the indicated antibiotics.
***The duration and need for combination therapy depend on the type of valve and causative organism.
Special populations
Elderly
Lower maintenance doses may be required due to age-related reduction in renal function.
Renal impairment
In pediatric and adult patients with renal impairment, consideration should be given to administering an initial dose followed by monitoring of vancomycin trough serum levels, rather than using a fixed scheduled dosing regimen, especially in patients with severe renal impairment or those undergoing renal replacement therapy (RRT), due to the many variable factors that may affect vancomycin levels in these patients.
In patients with mild or moderate renal impairment, the initial dose should not be reduced. In patients with severe renal impairment, it is preferable to prolong the dosing interval rather than administer lower daily doses.
Particular attention should be paid to the concomitant administration of medicinal products that may reduce vancomycin clearance and/or potentiate its adverse effects.
Vancomycin is poorly dialyzable by intermittent hemodialysis. However, the use of high-flux membranes and continuous renal replacement therapy (CRRT) increases vancomycin clearance and generally requires supplemental dosing (usually after the hemodialysis session in the case of intermittent hemodialysis).
Adults
Dose adjustments in adult patients may be based on estimated glomerular filtration rate (eGFR) using the following formula:
Men: [Weight (kg) × (140 – age (years))] / [72 × serum creatinine (mg/dL)]
Women: 0.85 × value calculated from the formula above.
The usual initial dose for adult patients is 15–20 mg/kg, which may be administered every 24 hours in patients with creatinine clearance between 20 and 49 mL/min. In patients with severe renal impairment (creatinine clearance <20 mL/min) or those undergoing renal replacement therapy, the appropriate timing and amount of subsequent doses largely depend on the RRT modality and should be based on serum vancomycin trough levels and residual renal function. Depending on the clinical situation, delaying the next dose until vancomycin level results are available may be considered.
In critically ill patients with renal impairment, the initial loading dose (25–30 mg/kg) should not be reduced.
Pediatric population
Dose adjustments in pediatric patients aged 1 year and older may be based on estimated glomerular filtration rate (eGFR) using the revised Schwartz formula:
eGFR (mL/min/1.73m²) = (height cm × 0.413) / serum creatinine (mg/dL)
eGFR (mL/min/1.73m²) = (height cm × 36.2) / serum creatinine (µmol/L)
For neonates and infants under 1 year of age, expert consultation should be sought, as the Schwartz formula is not applicable to them.
Guidance on dosing recommendations for the pediatric population are shown in the table below, following the same principles as for adult patients.

*The appropriate timing and amount of subsequent doses largely depend on the mode of RRT
and should be based on serum vancomycin levels obtained prior to dosing and residual renal
function. Depending on the clinical situation, consideration may be given to delaying the
next dose to await vancomycin level results.
Hepatic impairment
Dose adjustment is not required in patients with hepatic impairment.
Pregnancy
Significantly increased doses may be required to achieve therapeutic serum concentrations in pregnant women.
Obese patients
In obese patients, the initial dose should be individually adjusted according to total body weight as in non-obese patients.
Oral administration
Treatment of Clostridium difficile infection (CDI):
Patients aged 12 years and older
The recommended dose of vancomycin is 125 mg every 6 hours for 10 days for the first episode of non-severe CDI. This dose may be increased to 500 mg every 6 hours for 10 days in case of severe disease or complications. The maximum daily dose should not exceed 2 g.
In patients with multiple recurrences, consideration may be given to treating the current episode of CDI with vancomycin 125 mg four times daily for 10 days, followed by a gradual tapering down to 125 mg daily or an intermittent regimen, i.e., 125–500 mg/day every 2–3 days for at least 3 weeks.
Neonates, infants and children under 12 years of age
The recommended dose of vancomycin is 10 mg/kg orally every 6 hours for 10 days. The maximum daily dose should not exceed 2 g.
The duration of vancomycin treatment may need to be adjusted according to the clinical course of individual patients. When possible, the antibacterial agent suspected of causing CDI should be discontinued. Adequate fluid and electrolyte replacement should be ensured.
Monitoring of serum vancomycin concentrations
The frequency of therapeutic drug monitoring (TDM) should be individualized based on clinical status and response to treatment, ranging from daily sampling that may be required in some hemodynamically unstable patients, to at least once weekly in stable patients showing a response to therapy. In patients with normal renal function, serum vancomycin concentration should be monitored on the second day of treatment, immediately before the next dose.
In patients undergoing intermittent dialysis, vancomycin levels should generally be obtained prior to the start of the hemodialysis session.
Serum vancomycin concentration monitoring should be performed after oral administration in patients with inflammatory intestinal disorders.
The therapeutic trough level of vancomycin in blood should normally be 10–20 mg/L, depending on the site of infection and pathogen susceptibility. Trough values of 15–20 mg/L are generally recommended by clinical laboratories to better cover pathogens classified as susceptible with MIC ≥1 mg/L.
Model-based methods may be useful in predicting individual dose requirements to achieve adequate AUC. The model-based approach may be used both for calculating an individualized initial dose and for dose adjustments based on TDM results.
Method of administration
Intravenous administration
Vancomycin for intravenous use is generally administered as an intermittent infusion, and the dosing recommendations presented in this section for intravenous use correspond to this mode of administration.
Vancomycin will be administered only as a slow intravenous infusion lasting at least one hour or at a maximum rate of 10 mg/min (whichever is longer), sufficiently diluted (at least 100 mL per 500 mg or at least 200 mL per 1000 mg).
Patients whose fluid intake must be limited may also receive a solution of 500 mg/50 mL or 1000 mg/100 mL, although the risk of infusion-related adverse effects may be increased with these higher concentrations.
For information on solution preparation, see below.
Continuous infusion of vancomycin may be considered, e.g., in patients with unstable vancomycin clearance.
Oral administration
The appropriate oral dose may be diluted in a glass of water and administered to the patient for oral intake. In case of oral administration, sweet syrups may be added to the solution to improve taste. The diluted solution, in approximately 50 mL of water, may also be administered via a nasogastric tube.
Oral vancomycin hydrochloride is not effective for other types of infections apart from CDI.
Solution preparation
At the time of use, add 10 mL of sterile water for injection to the 500 mg vial of the medicinal product. The vial thus prepared will yield a solution of 50 mg/mL.
After reconstitution, vials may be stored in the refrigerator (between +2°C and +8°C) for 14 days without significant loss of potency.
Intermittent intravenous administration (preferred method)
The reconstituted solution containing 500 mg of vancomycin should be further diluted with at least 100 mL of 0.9% sodium chloride or 5% glucose solution.
The desired dose, so diluted, should be administered by intermittent intravenous infusion over a period of not less than 60 minutes and repeated at 6-hour intervals.
Continuous infusion administration (to be used only when intermittent administration is not feasible). Add the contents of the vial of solution, prepared as described above, to the volume of 0.9% sodium chloride or 5% glucose solution required to allow slow intravenous infusion over 24 hours.
Infusion-related events are related to both the concentration and the rate of vancomycin administration. In adults, a concentration not exceeding 5 mg/mL and an infusion rate below 10 mg/min are recommended. Concentrations up to 10 mg/mL may be used in patients requiring fluid restriction; the use of higher concentrations may increase the risk of infusion-related events.
Infusion-related events may, however, occur at any concentration or infusion rate.
Compatibility with other intravenous fluids
Reconstituted vancomycin further diluted with 5% dextrose solution or 0.9% sodium chloride solution may be stored refrigerated for 14 days without significant loss of activity.
Solutions further diluted with the following infusion fluids may be stored refrigerated for 96 hours:

• 5% dextrose solution and 0.9% sodium chloride solution
• Lactated Ringer's solution
• Lactated Ringer's solution and 5% dextrose solution
• Normosol-M with 5% dextrose
• Isolyte-E solution
• Ringer acetate solution

Vancomycin solution has a low pH and may cause physical instability of other compounds.
Prior to administration, parenterally administered medications should be inspected visually for particulate matter and/or discoloration whenever solution and container permit.
Incompatibilities
Mixtures of vancomycin solutions and beta-lactam antibiotics have been shown to be physically incompatible. The likelihood of precipitate formation increases with higher vancomycin concentrations. Adequate flushing of the intravenous line between administrations of these antibiotics is recommended. Dilution of vancomycin solutions to a concentration equal to or less than 5 mg/mL is also recommended.
Although intravitreal injection is not an approved route of administration for vancomycin, precipitate formation has been observed after injection of vancomycin and ceftazidime into the vitreous cavity for endophthalmitis, using separate syringes and needles. The precipitates gradually dissolved, with complete clearing of the vitreous cavity over more than two months and improvement in visual acuity.
Oral administration
Vancocina A.P. for injection may also be administered orally for the treatment of antibiotic-associated pseudomembranous colitis due to Clostridium difficile and in staphylococcal enterocolitis. In such cases, the contents of one vial (500 mg) may be diluted in approximately 50 mL of water and administered orally or via a nasogastric tube. To improve the taste of oral administration, sweet syrups may be added to the solution.
Overdose
Maintenance of glomerular filtration is recommended as supportive measure. Vancomycin is poorly removed by dialysis.
Increased vancomycin clearance has been achieved through hemofiltration and hemoperfusion with polysulfone resin.