Vancomicinum Delfarma

Leaflet accompanying the packaging: patient information

Warning! The leaflet should be kept. Information on the immediate packaging in a foreign language.

Vancomycinum Delfarma, 1 g, powder for solution for infusion and solution

for oral use
Vancomycinum

The leaflet should be read carefully before taking the medicine, as it contains important information for the patient.

• The leaflet should be kept so that it can be read again if necessary.
• In case of any doubts, the doctor or pharmacist should be consulted.
• This medicine has been prescribed to a specific person. It should not be given to others. The medicine may harm another person, even if the symptoms of their illness are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Vancomycinum Delfarma and what is it used for
• 2. Important information before taking Vancomycinum Delfarma
• 3. How to take Vancomycinum Delfarma
• 4. Possible side effects
• 5. How to store Vancomycinum Delfarma
• 6. Contents of the packaging and other information

1. What is Vancomycinum Delfarma and what is it used for

Vancomycin is an antibiotic belonging to the class of glycopeptide antibiotics. The action of vancomycin involves killing certain bacteria that cause infections. Vancomycin in powder form is used to prepare a solution for infusion or oral solution.

Indications for use

Intravenous use
Vancomycin is used in all age groups in the form of an infusion (drip) to treat the following severe infections:

• skin and subcutaneous tissue infections;
• bone and joint infections;
• lung infections, known as pneumonia;
• infections of the inner lining of the heart (endocarditis);
• blood infections related to the above-mentioned infections.

Oral use
Vancomycin may be given orally to adults and children to treat infections of the mucous membrane of the small and large intestine associated with damage to the mucous membrane (pseudomembranous colitis) caused by Clostridium difficile bacteria.

2. Important information before taking Vancomycinum Delfarma

When not to take Vancomycinum Delfarma

• if the patient is allergic to vancomycin or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

After injecting vancomycin into the eye, severe side effects have occurred, which can lead to vision loss.
Before starting treatment with Vancomycinum Delfarma, the patient should discuss with their doctor, hospital pharmacist, or nurse if:

• the patient has previously had an allergic reaction to teicoplanin, as this may indicate that the patient is also allergic to vancomycin.
• the patient has hearing problems, especially if they are elderly (hearing tests may be necessary during treatment).
• the patient has kidney problems (blood tests and kidney and liver function tests may be necessary during treatment).
• the patient is receiving vancomycin by infusion to treat diarrhea associated with Clostridium difficile infection, instead of oral administration.
• the patient has ever had a severe skin rash or peeling of the skin, blisters, and (or) ulcers of the mouth after taking vancomycin.

Severe skin reactions have occurred with vancomycin treatment, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP). If the patient notices any of the symptoms described in section 4, they should stop taking vancomycin and consult their doctor immediately.
During treatment with Vancomycinum Delfarma, the patient should discuss with their doctor, hospital pharmacist, or nurse if:

• the patient is taking vancomycin for a long time (blood tests and kidney and liver function tests may be necessary during treatment).
• the patient experiences any skin reaction during treatment.
• the patient experiences severe or prolonged diarrhea during or after vancomycin treatment; in such cases, the patient should consult their doctor immediately. This may be a sign of colitis (pseudomembranous colitis), which can occur during antibiotic treatment.

Children

Vancomycin will be used with special caution in premature infants and young infants, as their kidneys are not fully developed, which can lead to the accumulation of vancomycin in the blood. In this age group, blood tests may be necessary to monitor the concentration of vancomycin in the blood.
Concomitant administration of vancomycin and anesthetics in children is associated with the occurrence of skin redness (flushing) and allergic reactions. Additionally, concomitant use with other medicines, such as aminoglycoside antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen), or amphotericin B (a medicine used to treat fungal infections), may increase the risk of kidney damage, and more frequent blood tests and kidney function tests may be necessary.

Vancomycinum Delfarma and other medicines

The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
Special caution is necessary if the patient is taking other medicines that may interact with vancomycin, such as:

• nephrotoxic (kidney-damaging) medicines (e.g., piperacillin with tazobactam) and ototoxic (hearing-damaging) medicines - they may enhance each other's side effects; special caution is necessary when using aminoglycosides concomitantly with vancomycin or immediately after it;
• anesthetics - they may increase the risk of blood pressure drop, skin redness, flushing, hives, and itching (see section 4. Possible side effects);
• muscle relaxants - vancomycin may enhance and prolong the effects of medicines used during surgery to reduce muscle tension, e.g., succinylcholine (neuromuscular blockade).

Use in elderly patients

The natural decline in glomerular filtration rate that occurs with age may lead to increased vancomycin concentrations in the blood if the dose is not properly adjusted (see "Dosing in patients with renal impairment").

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor or pharmacist before taking this medicine.
There is insufficient observation regarding the use of vancomycin during pregnancy and breastfeeding in humans. Vancomycin can be given to pregnant women only when the benefit to the mother outweighs the potential risk to the fetus.
Animal studies have not shown any effect of the medicine on the occurrence of developmental abnormalities.
Vancomycin passes into human milk, and therefore, breastfeeding should be discontinued during treatment with this medicine, as side effects may occur in the breastfed child.

Driving and operating machinery

No data available.

3. How to take Vancomycinum Delfarma

The patient will receive Vancomycinum Delfarma administered by medical staff during their hospital stay. The doctor will decide what dose of the medicine the patient should receive each day and how long the treatment should last.

Dosage

The administered dose will depend on:

• the patient's age,
• the patient's body weight,
• the type of infection,
• kidney function,
• the patient's hearing,
• any other medicines the patient is taking.

Intravenous administration

Adults and adolescents (12 years and older)

The dosage will be determined based on the patient's body weight. The usual dose used in infusion is 15 to 20 mg per kilogram of body weight. This dose is usually administered every 8 to 12 hours.
In some cases, the doctor may decide to use a loading dose of 30 mg per kilogram of body weight. The maximum daily dose should not exceed 2 g.

Use in children

Children from the first month of life and children under 12 years of age
The dosage will be determined based on the patient's body weight. The usual dose used in infusion is 10 to 15 mg per kilogram of body weight. This dose is usually administered every 6 hours.
Preterm and full-term newborns (from 0 to 27 days of post-conceptional age)
The dose will be calculated based on post-conceptional age [the time from the first day of the last menstrual period to birth (gestational age) plus the time from birth (postnatal age)].

Oral administration

Adults and adolescents (12 to 18 years old)

The recommended dose is 125 mg every 6 hours. In some cases, the doctor may decide to use a higher daily dose, up to 500 mg every 6 hours. The maximum daily dose should not exceed 2 g.
If the patient has had other disorders (mucous membrane infection), a different dose and duration of treatment may be necessary.

Use in children

Newborns, infants, and children under 12 years of age
The recommended dose is 10 mg per kilogram of body weight. This dose is usually administered every 6 hours.
The maximum daily dose should not exceed 2 g.

Method of administration

Intravenous infusion (drip) means that the medicine flows from a bottle or infusion bag through a tube into one of the patient's veins. The doctor or nurse will always administer vancomycin into the blood, not into the muscle.
Vancomycin will be administered into a vein over at least 60 minutes.
Method of oral administration
In case of treatment of gastrointestinal disorders (so-called pseudomembranous colitis), the medicine must be administered in the form of an oral solution (the patient will take the medicine orally).
The contents of one vial of Vancomycinum Delfarma should be dissolved in 20 ml of water. Single doses can be drawn (e.g., 2.5 ml = 125 mg of vancomycin) and administered to the patient in a slightly diluted form or introduced through a gastric tube.
A flavor enhancer, such as commonly used syrups, can be added to the prepared solution before administration.
Method of intravenous administration
Detailed instructions are provided at the end of the leaflet, in the section "Information intended exclusively for healthcare professionals".
Duration of treatment
The duration of treatment depends on the type of infection and may last several weeks.
The duration of treatment may vary depending on the patient's response to treatment.
During treatment, the patient may undergo blood tests and urine analysis, and may also undergo a hearing test to monitor for potential side effects.

Overdose of Vancomycinum Delfarma

Treatment used in case of overdose:

• a specific antidote is not known;
• high vancomycin concentrations in the blood can be effectively reduced using hemodialysis with polysulfone membranes, as well as hemofiltration or hemoperfusion with polysulfone resins;
• in case of overdose, symptomatic treatment and maintenance of kidney function are necessary. If a higher dose of the medicine is taken, the patient should immediately consult their doctor or pharmacist.

Missed dose of Vancomycinum Delfarma

A double dose should not be taken to make up for a missed dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If the patient notices any of the following symptoms, they should stop taking vancomycin and consult their doctor immediately:

• red, flat, target-like, or round spots on the torso, often with blisters in the center, peeling of the skin, ulcers of the mouth, throat, nose, genitals, and eyes. The occurrence of these severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome and toxic epidermal necrolysis).
• widespread rash, high fever, and swollen lymph nodes (DRESS or drug reaction with eosinophilia and systemic symptoms).
• red, peeling rash with bumps under the skin and blisters, accompanied by fever at the beginning of treatment (acute generalized exanthematous pustulosis).

Vancomycin may cause allergic reactions, but severe allergic reactions (anaphylactic reactions) are rare. If the patient suddenly experiences wheezing, difficulty breathing, redness of the upper body, rash, or itching, they should immediately

inform their doctor.
Vancomycin absorption from the gastrointestinal tract is negligible. However, if the patient has an inflammatory disease of the gastrointestinal tract, and especially if they also have kidney problems, side effects may occur that are similar to those that occur after intravenous administration of vancomycin.

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

• low blood pressure,
• shortness of breath, wheezing (a high-pitched sound caused by obstruction of the airway),
• rash and inflammation of the mucous membrane of the mouth, itching, itchy rash, hives,
• kidney problems, usually detectable in blood tests,
• redness of the upper body and face, vein inflammation.

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 the number of white blood cells, red blood cells, and platelets (blood cells responsible for blood clotting),

increase in the number of certain white blood cells in the blood,

• balance disorders, ringing in the ears, dizziness,
• inflammation of blood vessels,
• nausea (vomiting)
• 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 occurrence of a severe allergic skin reaction, including peeling of the skin or blistering. This may be accompanied by high fever and joint pain.
• cardiac arrest,
• inflammation of the intestine causing abdominal pain and diarrhea, which may contain blood.

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

• vomiting, diarrhea,
• confusion, drowsiness, lack of energy, swelling, fluid retention, decreased urine production,
• rash with swelling and pain in the area behind the ears, neck, armpits, under the chin and under the arms (lymph node swelling), abnormal blood test results and liver function tests,
• rash with blisters and fever.

Reporting side effects

If side effects occur, including any side effects not listed in the leaflet, the patient should inform their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Drug Safety of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl
Reporting side effects will help gather more information on the safety of this medicine.

5. How to store Vancomycinum Delfarma

The medicine should be stored out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month.
Do not store above 25°C.
Stability of the solution
The product should be used immediately after reconstitution/dilution. If not used immediately, the user is responsible for the conditions and duration of storage before use; usually, the storage period should not exceed 24 hours, and the product should be stored at a temperature between 2°C and 8°C, unless reconstitution/dilution was performed in controlled and approved aseptic conditions.
The prepared solution remains stable for 4 days at a temperature between 2°C and 8°C and for 2 days at a temperature between 20°C and 25°C.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Vancomycinum Delfarma contains

• The active substance of the medicine is vancomycin. 1 vial contains 1 g of vancomycin (in the form of 1020 mg of vancomycin hydrochloride), which corresponds to 1,000,000 IU of vancomycin.

The medicine does not contain any other ingredients.

What Vancomycinum Delfarma looks like and what the packaging contains

Depending on the crystal structure of the active substance, the lyophilizate may have a color from white to slightly pink or even brownish.
A vial made of colorless glass, in a cardboard box, containing 1 vial.
To obtain more detailed information, the patient should contact the marketing authorization holder or parallel importer.

Marketing authorization holder in Italy, the country of export:

Pharmatex Italia S.r.l.
Via S. Paolo, 1 - 20121 Milan, Italy

Manufacturer:

Fisiopharma S.r.l.
Nucleo Industriale, 84020 Palomonte (SA), Italy

Parallel importer:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź

Repackaged by:

Delfarma Sp. z o.o.
ul. Św. Teresy od Dzieciątka Jezus 111, 91-222 Łódź
Italian marketing authorization number: 034632024

Parallel import authorization number: 285/24

Date of leaflet approval: 11.07.2024

Medical advice and education

Antibiotics are used to treat bacterial infections. They are ineffective against viral infections.
If a doctor has prescribed antibiotics to the patient, they are necessary to treat a specific current illness.
Despite antibiotic treatment, some bacteria may survive or multiply. This phenomenon is called resistance; it can make antibiotic treatment ineffective.
Improper use of antibiotics promotes the development of resistance. The patient can also facilitate the development of resistance and thus delay recovery or reduce the effectiveness of antibiotic therapy if they do not follow the proper:

• dosing,
• treatment schedule,
• duration of treatment. To maintain the effectiveness of this medicine, the patient should:
• 1 - take antibiotics only when prescribed by a doctor.
• 2 - strictly follow the prescribed method of administration.
• 3 - not take an antibiotic again without the doctor's recommendation, even to treat a similar illness.

Information intended exclusively for healthcare professionals

Spectrum of antibacterial activity
Vancomycin is active against Gram-positive bacteria, such as staphylococci, streptococci, enterococci, pneumococci, and Clostridium. Gram-negative bacteria are resistant.
In some cases, an increasing number of resistance cases are observed, especially among enterococci; the occurrence of multi-drug resistant Enterococcus faecium strains is particularly concerning.
Cross-resistance occurs with other glycopeptide antibiotics, such as teicoplanin.
Bacterial cultures should be taken to isolate and identify the causative microorganisms and determine their susceptibility to vancomycin.
Dosage
In appropriate cases, vancomycin should be used in combination with other antibacterial products.

Intravenous administration

The initial dose should be determined based on the total body weight. Subsequent modifications of the dose should be based on the concentration of vancomycin in the serum, with the aim of achieving the target therapeutic concentration. When determining subsequent doses and intervals between them, kidney function should also be taken into account.
Patients 12 years and older
The recommended dose is 15 to 20 mg/kg every 8 to 12 hours (do not exceed 2 g per dose).
In the case of patients in severe condition, a loading dose of 25-30 mg/kg may be used to facilitate rapid achievement of the target minimum vancomycin concentration in the serum.
Newborns from the first month of life and children under 12 years of age:
The recommended dose is 10 to 15 mg/kg every 6 hours.
Full-term newborns (from birth to 27 days of postnatal age) and preterm infants (from birth to the expected date of delivery plus 27 days)
To determine the dosing schedule for newborns, the patient should consult a doctor experienced in treating newborns. One possible dosing schedule for vancomycin in newborns is presented in the table below:
PMA: post-conceptional age [the time from the first day of the last menstrual period to birth (gestational age) plus the time from birth (postnatal age)].

* Continue until it is no longer necessary to remove necrotic tissue, the patient's clinical condition improves, and the patient has not had a fever for 48-72 hours.
** In the case of prosthetic joint infections, longer cycles of oral suppressive therapy with appropriate antibiotics for prosthetic joint infections should be considered.
*** The duration and need for combination therapy depend on the type of valve and microorganism.
Special patient groups
Elderly patients
Due to the age-related limitation of kidney function, it may be necessary to use lower maintenance doses.
Patients with renal impairment
In adult and pediatric patients with renal impairment, the initial loading dose should be considered, and then the concentration of vancomycin in the serum should be determined, rather than the planned treatment schedule, especially in patients with severe renal impairment or undergoing renal replacement therapy (RRT), due to the many variables that affect vancomycin concentrations in such 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 extend the intervals between doses rather than administer lower doses.
Concomitantly administered medicines that may decrease vancomycin clearance and (or) enhance its side effects should be properly evaluated.
Vancomycin is poorly removed by intermittent hemodialysis. However, the use of high-flux filtration membranes or continuous renal replacement therapy (CRRT) increases vancomycin clearance, and it is essentially necessary to administer supplemental doses (usually after a hemodialysis session, in the case of intermittent hemodialysis).
Adult patients
Dose modifications in adult patients may be based on the estimated glomerular filtration rate (eGFR) using the following formula:
Men: [Weight (kg) x 140 - age (years)] / 72 x serum creatinine concentration (mg/dl)
Women: 0.85 x the value calculated using the above formula.
Usual initial dose for adult patients is 15 to 20 mg/kg; this dose can be administered every 24 hours to patients with a creatinine clearance of 20 to 49 ml/min. In patients with severe renal impairment (creatinine clearance below 20 ml/min) or patients undergoing renal replacement therapy, the appropriate intervals between doses and the size of subsequent doses largely depend on the RRT method used and should be determined based on vancomycin serum concentration values and residual renal function.
Depending on the clinical situation, it may be considered to withhold the next dose until the vancomycin concentration in the blood is determined.
In critically ill patients with renal impairment, the initial loading dose should not be reduced.
Children and adolescents
Dose modifications in children and adolescents 1 year of age and older may be based on the estimated glomerular filtration rate (eGFR) using the modified Schwartz formula:
eGFR (ml/min/1.73m^2) = (height in cm x 0.413) / serum creatinine concentration (mg/dl)
eGFR (ml/min/1.73m^2) = (height in cm x 36.2) / serum creatinine concentration (μmol/l)
For newborns and infants under 1 year of age, the patient should consult an expert, as the Schwartz formula does not apply to such patients.
Guidelines for dosing in children and adolescents are subject to the same rules as those for adult patients.

*The appropriate intervals between doses and the size of subsequent doses largely depend on the RRT method used and should be determined based on vancomycin serum concentration values and residual renal function. Depending on the clinical situation, it may be considered to withhold the next dose until the vancomycin concentration in the blood is determined.
Patients with hepatic impairment:
There is no need to adjust the dose in patients with mild hepatic impairment.
Pregnancy
In the case of pregnant women, it may be necessary to significantly increase the doses to achieve therapeutic serum concentrations.
Obese patients
In obese patients, the initial dose should be adjusted individually based on the total body weight, just like in patients with normal body weight.

Oral administration

Patients 12 years and older
Treatment of Clostridium difficile infection (CDI).
The recommended dose of vancomycin is 125 mg every 6 hours for 10 days in the case of the first episode of non-severe CDI. The dose may be increased to 500 mg every 6 hours for 10 days in the case of severe or complicated disease. The maximum daily dose should not exceed 2 g.
In patients with multiple recurrences, it may be considered to treat the current episode of CDI with vancomycin at a dose of 125 mg four times a day for 10 days, followed by a gradual reduction of the dose to 125 mg per day or the use of a pulsing regimen, i.e., 125-500 mg/day every 2-3 days for at least 3 weeks.
Newborns, infants, and children under 12 years of age
The recommended dose of vancomycin is 10 mg/kg every 6 hours for 10 days. The maximum daily dose should not exceed 2 g.
The duration of treatment with vancomycin may need to be adjusted according to the clinical course of the disease in each case. Whenever possible, the use of the suspected antibacterial product should be discontinued. Adequate fluid and electrolyte supplementation should be ensured.
Monitoring of vancomycin serum concentration
The frequency of therapeutic drug monitoring (TDM) should be adjusted individually according to the clinical situation and response to treatment; the frequency of sampling may range from daily in some unstable hemodynamic patients to once a week in stable patients with a visible response to treatment. In patients with normal kidney function, the vancomycin serum concentration should be determined on the second day of treatment, immediately before the next dose.
In patients undergoing intermittent hemodialysis, the vancomycin concentration should be determined before the start of the hemodialysis session.
Monitoring of vancomycin serum concentration after oral administration should be performed in patients with inflammatory diseases of the intestine.
The minimum therapeutic vancomycin concentration in the blood should be 10-20 mg/l, depending on the site of infection and the susceptibility of the pathogen. Clinical laboratories usually recommend a minimum concentration of 15-20 mg/l, ensuring better coverage of microorganisms classified as susceptible with an MIC ≥1 mg/l.
In predicting individual dosing required to achieve the appropriate AUC value, model-based methods may be useful. A model-based approach can be applied when calculating the individual initial dose and when modifying doses based on TDM results.
Method of administration
Intravenous administration
Vancomycin is usually administered intravenously in the form of an intermittent infusion; the dosing recommendations provided in this section for the intravenous route refer to this method of administration.

Preparation of the solution

Before use, the dry substance should be dissolved in water for injection. The resulting solution should be further diluted with compatible injection solutions (see "Incompatibilities" below).
The contents of a vial of Vancomycinum Delfarma should be dissolved in 20 ml of water for injection, and then further diluted with other infusion solutions to at least 200 ml.
The powder should be dissolved in such an amount of solvent that the concentration of the infusion solution does not exceed 5 mg/ml (i.e., 1 g/200 ml).
It may be considered to use continuous infusion of vancomycin, e.g., in patients with unstable vancomycin clearance.
Oral administration
The contents of one vial of Vancomycinum Delfarma should be dissolved in 20 ml of water.
Single doses can be drawn from the prepared solution (e.g., 2.5 ml = 125 mg of vancomycin) and administered to the patient in a slightly diluted form or introduced through a gastric tube.
A flavor enhancer, such as commonly used syrups, can be added to the solution before administration.
Incompatibilities
Vancomycin solutions have a low pH value. Mixing them with other substances can lead to chemical or physical instability. Any solution for parenteral administration should be inspected for precipitates and discoloration before use. Turbidity of the solution occurs when the vancomycin solution is mixed with the following substances:
aminophylline, barbiturates, benzylpenicillin, chloramphenicol sodium succinate, chlorothiazide sodium salt, dexamethasone 21-disodium phosphate, heparin sodium salt, hydrocortisone 21-sodium succinate, methicillin sodium salt, sodium bicarbonate, nitrofurantoin sodium salt, novobiocin sodium salt, phenytoin sodium salt, sulfadiazine sodium salt, sulfafurazole diethanolamine salt.
Compatibility with infusion fluids
The following infusion fluids can be used to prepare the infusion solution:

• water for injection - only for dissolving the powder;
• 5% glucose solution;
• 0.9% NaCl solution;
• 5% glucose solution with 0.9% NaCl solution.

The vancomycin solution should be administered separately, unless its physicochemical compatibility with the given injection solution has been demonstrated.
Combination therapy
If combination therapy with vancomycin and other antibiotics or chemotherapeutic agents is used, these products should be administered separately.