Vancomycin polpharma

Patient Information Leaflet

Warning! Keep this leaflet. The information on the immediate packaging is in a foreign language.
Vancomycin Polpharma (Vancomicina Azevedos), 500 mg, powder for preparation of
concentrate for infusion solution
Vancomycinum
Vancomycin Polpharma and Vancomicina Azevedos are different brand names for the same
medicinal product.
Please read this leaflet carefully before using this medicine, as it contains important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents:

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

1. What Vancomycin Polpharma is and what it is used for

Vancomycin is an antibiotic belonging to the class of glycopeptide antibiotics. Vancomycin works by killing certain bacteria that cause infections.
Vancomycin in powder form is used to prepare a concentrate for infusion solution or an oral solution.
Vancomycin is administered intravenously (by infusion) in all age groups for the treatment of the following serious infections:

• skin and soft tissue infections;
• bone and joint infections;
• lung infections known as pneumonia;
• infections of the inner lining of the heart (endocarditis), and prevention of bacterial endocarditis in high-risk patients undergoing major surgical procedures;
• central nervous system infections;
• bloodstream infections associated with the above-mentioned infections.

Oral vancomycin may be used in adults and children for the treatment of infection of the intestinal mucosa of the small and large intestine associated with mucosal damage (pseudomembranous colitis), caused by Clostridium difficile bacteria.

2. Important information before using Vancomycin Polpharma

When not to use Vancomycin Polpharma

• if the patient is allergic to vancomycin.

Warnings and precautions
Severe adverse reactions, potentially leading to loss of vision, have occurred after injection of vancomycin into the eye.
Before starting treatment with Vancomycin Polpharma, discuss this with the doctor, hospital pharmacist, or nurse if:

• the patient has previously experienced an allergic reaction to teicoplanin, as this may indicate that the patient is also allergic to vancomycin;
• the patient has hearing problems, especially if elderly (hearing tests may be necessary during treatment);
• the patient has impaired kidney function (blood tests and liver and kidney function tests may be required during treatment);
• the patient is receiving vancomycin by infusion to treat diarrhea associated with Clostridium difficile infection, rather than oral administration;
• the patient has ever experienced severe skin rash, skin peeling, blisters, and/or oral mucosal ulcers after receiving vancomycin.

Serious skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have been reported during vancomycin therapy. If the patient notices any of the symptoms described in section 4, vancomycin should be discontinued immediately and medical advice should be sought without delay.

During treatment with Vancomycin Polpharma, discuss with the doctor, hospital pharmacist, or nurse if:

• the patient is receiving vancomycin for a prolonged period (blood tests and liver and kidney function tests may be necessary during treatment);
• the patient develops any skin reaction during treatment;
• the patient develops severe or persistent diarrhea during or after completion of vancomycin therapy; in such a case, immediate medical consultation is required. This may be a sign of intestinal inflammation (pseudomembranous colitis), which may occur during antibiotic treatment.

Children
Vancomycin should be used with particular caution in premature infants and young children, as their kidneys are not fully developed, which may lead to accumulation of vancomycin in the blood. In this age group, blood tests may be necessary to monitor vancomycin blood levels.
Concomitant administration of vancomycin and anesthetic agents in children has been associated with skin flushing (erythema) and allergic reactions. Additionally, concurrent use with other medications such as aminoglycoside antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen), or amphotericin B (used in fungal infections) may increase the risk of kidney damage, and therefore more frequent blood and kidney function tests may be required.

Vancomycin Polpharma and other medicines
Inform the doctor, pharmacist, or nurse about all medicines currently used, recently used, or planned for use.
Particular caution is required if the patient is taking other medicines that may interact with vancomycin, for example:

• Concomitant use of vancomycin and anesthetic agents may cause hypotension, shortness of breath, skin flushing, urticaria, and itching; it may also cause a strong reaction resembling an allergic reaction. The incidence of these effects is lower when vancomycin is administered by slow intravenous infusion before the anesthetic agent.
• When vancomycin is used concomitantly with drugs that may damage hearing, nerves, and/or kidneys (especially: ethacrynic acid, aminoglycoside antibiotics, amphotericin B, bacitracin, polymyxin B, piperacillin with tazobactam, colistin, viomycin, or cisplatin), the doctor will closely monitor the patient's condition.
• The doctor will exercise particular caution when vancomycin is used concomitantly with muscle relaxants.

Pregnancy, breastfeeding, and effects on fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning a pregnancy, she should consult a doctor before using this medicine.
Vancomycin may be administered during pregnancy only if absolutely necessary and when, in the doctor's opinion, the benefits outweigh the risks. The doctor may recommend monitoring serum vancomycin levels to reduce the risk of toxic effects on the fetus.
Vancomycin passes into human milk; therefore, it may be used during breastfeeding only if other antibiotics have proven ineffective. If treatment of the mother with vancomycin is absolutely necessary, the doctor will carefully monitor the infant or may recommend discontinuation of breastfeeding.
There are no studies on the effect of vancomycin on fertility.

Driving and operating machinery
Vancomycin Polpharma has negligible influence on the ability to drive vehicles or operate machinery.

3. How to use Vancomycin Polpharma

The patient will receive Vancomycin Polpharma administered by medical personnel during
their hospital stay. The doctor will decide the daily dose required and the duration of treatment.
Dosage
The dose administered will depend on:

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

Intravenous administration
Adults and adolescents (aged 12 years and older)
The dosage will be determined based on the patient's body weight. The usual dose administered by infusion is 15 to 20 mg per kg of body weight. This dose is usually given every 8 to 12 hours. In certain cases, the doctor may decide to use an initial dose of up to 30 mg per kg of body weight. The maximum daily dose of vancomycin should not exceed 2 g.

Use in children
Children from 1 month of age and children under 12 years of age
Dosage will be determined based on the patient's body weight. The usual dose administered by infusion is 10 to 15 mg per kg of body weight. This dose is usually given every 6 hours.

Preterm and full-term newborns (0 to 27 days)
The dose will be calculated based on postmenstrual age [the time elapsed from the first day of the mother's last menstrual period to delivery (gestational age) plus the time elapsed since birth (postnatal age)].

In elderly patients, pregnant women, and patients with impaired kidney function (including dialysis patients), a different dosage may be required.

Oral administration
Adults and adolescents (aged 12 years and older)
The recommended dose is 125 mg every 6 hours. In certain cases, the doctor may decide to use a higher daily dose, up to a maximum of 500 mg every 6 hours. The maximum daily dose should not exceed 2 g.
If the patient has previously had other disorders (mucosal infection), a different dosage and duration of treatment may be required.

Use in children
Newborns, infants, and children under 12 years of age
The recommended dose is 10 mg per kg 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 bloodstream, never into muscle.
Vancomycin will be administered into a vein over at least 60 minutes.

When used in the treatment of gastrointestinal disorders (so-called pseudomembranous colitis), the medicine must be given in the form of an oral solution (the patient will take the medicine orally).
Instructions for preparing the solution prior to administration are provided in the section "Information intended exclusively for healthcare professionals" at the end of this leaflet.

Duration of treatment
The duration of treatment depends on the type of infection present in the patient and may last several weeks.
The duration of treatment may vary depending on the individual patient's response to therapy.
During treatment, blood tests and urine analyses may be performed, and hearing tests may be conducted to monitor for potential adverse effects.

If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like any medicine, this medicine may cause adverse reactions, although not everyone will experience them.
Vancomycin may cause allergic reactions, but severe allergic reactions (anaphylactic reactions) are rare. If the patient suddenly develops wheezing, difficulty breathing, redness of the upper body, rash or itching, the attending physician should be informed immediately.
If the patient notices any of the following symptoms, vancomycin should be discontinued and medical advice should be sought immediately:

• red, flat lesions on the trunk resembling target lesions or circular rashes, often with central blisters, skin peeling, and ulceration of the mouth, throat, nose, genital organs, and eyes. 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 enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
• red, scaly rash with subcutaneous nodules and blisters accompanied by fever at the beginning of treatment (acute generalized exanthematous pustulosis, see section 2 "Warnings and precautions").

Common adverse reactions (may occur in up to 1 in 10 patients):

• decrease in blood pressure
• shortness of breath, wheezing (a high-pitched sound caused by an obstruction in the upper airways)
• rash and inflammation of the oral mucosa, itching, itchy rash, urticaria
• kidney function disturbances detected usually in blood tests
• redness of the upper body and face, phlebitis

Uncommon adverse reactions (may occur in up to 1 in 100 patients):

• transient or permanent hearing loss

Rare adverse reactions (may occur in up to 1 in 1,000 patients):

• decrease in the number of white blood cells, red blood cells, and platelets (blood cells responsible for blood clotting)
• increase in certain white blood cells in the blood
• disturbances in balance, tinnitus, dizziness
• vasculitis
• nausea
• kidney inflammation and kidney failure
• chest and back muscle pain
• fever, chills

Very rare adverse reactions (may occur in up to 1 in 10,000 patients):

• sudden onset of severe allergic skin reaction involving skin peeling or blistering. This may be accompanied by high fever and joint pain.
• cardiac arrest
• intestinal inflammation causing abdominal pain and diarrhoea, which may contain blood.

Frequency unknown (frequency cannot be estimated from the available data)

• vomiting, diarrhoea
• confusion, drowsiness, lack of energy, oedema, fluid retention, reduced urine output
• rash with swelling and pain behind the ears, neck, groin, under the chin and under the arms (lymph node swelling), abnormal blood test results and liver function abnormalities
• blistering rash with fever

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions 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 adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Vancomycin Polpharma

• Keep this medicine out of sight and reach of children.
• Do not use after the expiry date stated on the container following the label "EXP". The expiry date refers to the last day of the specified month.
• Store below 25°C.
• Keep in the original packaging.
• Storage of solutions: see "Preparation of infusion solution" at the end of the leaflet, in the section intended for healthcare personnel.
• Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Vancomycin Polpharma contains
The active substance is vancomycin in the form of vancomycin hydrochloride. Each vial contains 500 mg of vancomycin. Vancomycin Polpharma does not contain any other ingredients.
What Vancomycin Polpharma looks like and contents of the pack
Vancomycin Polpharma is a white or slightly brownish powder.
Vial made of colourless type I glass, with a rubber stopper and aluminium cap, in a cardboard box.
The pack contains 10 vials.
For further information, please contact the responsible party or the parallel importer.
Responsible party in Portugal, country of export:
Laboratórios Azevedos – Indústria Farmacêutica, S.A.
Estrada Nacional 117-2, Alfragide
2614-503 Amadora
Portugal
Manufacturer:
Sofarimex – Indústria Química e Farmacêutica, S.A.
Av. das Indústrias, Alto de Colaride
2735-213 Cacém
Portugal
Parallel importer:
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19
83-200 Starogard Gdański
Repackaged in:
CEFEA Sp. z o.o. Sp. komandytowa
ul. Działkowa 56
02-234 Warsaw
LABOR Przedsiębiorstwo Farmaceutyczno-Chemiczne Sp. z o.o.
ul. Długosza 49
51-162 Wrocław
Portugal marketing authorisation number, country of export: 5623707
Parallel import authorisation number: 292/24
(logo of the parallel importer)

Information intended exclusively for healthcare professionals

The medicinal product should be administered by intravenous infusion or orally. It must not be given as a rapid intravenous bolus injection or by intramuscular injection.
Intravenous administration
The initial dose should be based on total body weight. Subsequent dose adjustments should be guided by serum concentrations with the aim of achieving the target therapeutic concentration. Renal function should also be taken into account when determining subsequent doses and dosing intervals.
The following dosing regimens are recommended:
Patients aged 12 years and older
The recommended dose is 15 to 20 mg/kg body weight every 8 to 12 hours (doses greater than 2 g per dose should not be used).
In critically ill patients, a loading dose of 25–30 mg/kg body weight may be used to facilitate rapid achievement of the target minimum serum vancomycin concentration.
Infants from one month of age and children under 12 years of age
The recommended intravenous dose is 10 to 15 mg/kg body weight every 6 hours.
Term neonates (from birth to 27 days postnatal age) and preterm neonates (from birth to expected date of delivery plus 27 days)
To determine the appropriate dosing regimen for neonates, advice should be sought from a physician experienced in treating neonates. One possible vancomycin dosing regimen for neonates is presented in the table below:

PMA: postconceptional age [time elapsed from the first day of the last menstrual period to birth (gestational age) plus time elapsed since birth (postnatal age)].
Duration of treatment
The recommended duration of treatment is given in the table below. In each case, the duration of treatment should be adjusted according to the type and severity of infection and the individual clinical response.

* Continue until no further removal of necrotic tissue is required,
the patient's clinical condition has improved, and the patient has been afebrile for 48 to 72 hours.
** In cases of prosthetic joint infections, longer cycles of oral suppressive antibiotic therapy should be considered.
*** The duration and need for combination therapy depend on the type of prosthesis and the microorganism involved.

Elderly patients
Due to age-related reduction in renal function, lower maintenance doses may be necessary.

Patients with renal impairment
In adult and pediatric patients with impaired renal function, an initial loading dose should be considered, followed by serum trough vancomycin concentration monitoring, rather than following a fixed dosing schedule—especially in patients with severe renal impairment or undergoing renal replacement therapy—due to multiple variable factors affecting 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, prolonging the dosing interval is preferred over administering smaller doses.

Concomitantly administered medicinal products that may reduce vancomycin clearance and/or increase its adverse effects should be carefully evaluated.

Vancomycin is only minimally removed by intermittent hemodialysis. However, the use of high-flux dialysis membranes or continuous renal replacement therapy (CRRT) increases vancomycin clearance, and supplemental doses are generally required (usually administered after the hemodialysis session in the case of intermittent hemodialysis).

Adult patients
Dose adjustments in adult patients may be based on estimated glomerular filtration rate (eGFR) calculated using the following formula:
Men: [weight (kg) × (140 − age (years))] / [72 × serum creatinine (mg/dL)]
Women: 0.85 × value calculated using the formula above

The usual initial dose in adult patients is 15 to 20 mg/kg body weight; this dose may 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 < 20 mL/min) or those undergoing renal replacement therapy, appropriate dosing intervals and dose amounts largely depend on the RRT modality used and should be determined based on serum vancomycin trough concentrations and residual renal function. Depending on the clinical situation, administration of the next dose may be withheld until vancomycin serum concentration results are available.

In critically ill patients with renal impairment, the initial loading dose (25 to 30 mg/kg body weight) should not be reduced.

Children and adolescents
Dose adjustments in children aged 1 year and older and in adolescents may be based on estimated glomerular filtration rate (eGFR) using the modified Schwartz formula:
eGFR (mL/min/1.73 m²) = (height in cm × 0.413) / serum creatinine (mg/dL)
eGFR (mL/min/1.73 m²) = (height in cm × 36.2) / serum creatinine (μmol/L)

For neonates and infants under 1 year of age, expert consultation is recommended, as the Schwartz formula is not applicable in these patients.

General dosing recommendations for children and adolescents provided in the table below follow the same principles as those for adult patients.

* Appropriate intervals between doses and the size of subsequent doses largely depend on
the RRT method used and should be determined based on serum vancomycin concentrations prior to administration and residual renal function. Depending on the clinical situation, consideration may be given to withholding the next dose until serum vancomycin concentration is measured.
Patients with hepatic impairment
Dose adjustment is not necessary in patients with liver dysfunction.
Pregnancy
In pregnant women, significantly increased doses may be required to achieve therapeutic serum vancomycin concentrations.
Obese patients
In obese patients, the initial dose should be individually adjusted according to total body weight, just as in patients with normal body weight.
Oral administration
Patients aged 12 years and older
Treatment of infections caused by Clostridium difficile (CDI)
For the first episode of non-severe CDI, the recommended vancomycin dose is 125 mg every
6 hours for 10 days. This dose may be increased to 500 mg every 6 hours for 10 days in cases of severe or complicated disease. The maximum daily dose should not exceed 2 g.
In patients with multiple recurrences, treatment of the current CDI episode may be considered with vancomycin 125 mg four times daily for 10 days, followed by a gradual dose reduction down to 125 mg daily or use of a pulsed 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 vancomycin dose is 10 mg/kg body weight every 6 hours for 10 days. The maximum daily dose should not exceed 2 g.
Adjustment of the duration of vancomycin treatment according to the individual clinical course of the disease may be necessary. Whenever possible, the antibacterial agent suspected of causing CDI should be discontinued. Adequate fluid and electrolyte replacement should be ensured.
Monitoring serum vancomycin concentration
The frequency of monitoring therapeutic drug concentration should be individually adjusted according to the clinical situation and response to treatment; sampling frequency may range from daily sampling in some hemodynamically unstable patients to at least once weekly in stable patients showing a clear response to therapy. In patients undergoing intermittent hemodialysis, vancomycin concentration should be measured before starting a hemodialysis session.
Serum vancomycin concentration monitoring after oral administration should be performed in patients with inflammatory bowel diseases.
The minimum therapeutic blood vancomycin concentration should be 10–20 mg/L, depending on the site of infection and pathogen susceptibility. 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 an appropriate AUC value, model-based methods may be useful. Model-based approaches can be applied both in calculating the initial individual dose and in modifying doses based on TDM results.
Method of administration
Intravenous administration
Vancomycin is usually administered intravenously as an intermittent infusion; the dosing recommendations provided in this section for the intravenous route refer to this method of administration.
Vancomycin should be administered exclusively as a slow intravenous infusion lasting at least one hour or at a maximum rate of 10 mg/min (longer duration) in a sufficiently diluted solution (at least 100 mL per 500 mg).
Patients with restricted fluid intake may receive a 500 mg/50 mL solution; however, with such higher concentration, the risk of infusion-related adverse reactions increases.
Continuous infusion of vancomycin may be considered, e.g., in patients with unstable vancomycin clearance.
Oral administration
The contents of the vial may be used to prepare an oral solution. The oral solution is prepared by dissolving the contents of the vial (500 mg vancomycin) in 30 mL of water. The appropriate dose can then be administered orally or via a nasogastric tube. Syrup may be added to the solution to improve taste.
Preparation of infusion solution
The contents of the vial should be dissolved in 10 mL of water for injections.
1 mL of the resulting solution contains 50 mg of vancomycin. The solution may be further diluted depending on the route of administration.
Multiple infusions
The prepared solution should be diluted in 100 mL of 5% glucose solution or 0.9% sodium chloride solution. The vancomycin concentration in the resulting solution should not exceed 5 mg/mL. The solution should be administered slowly intravenously, at a maximum rate of 10 mg/min, over at least 60 minutes.
Continuous infusion
Should only be used when multiple infusions are not feasible. The vancomycin solution with a concentration of 50 mg/mL should be diluted in such a volume of 5% glucose solution or 0.9% sodium chloride solution that the patient receives the prescribed daily dose as a continuous 24-hour infusion.
Stability and storage conditions of solutions
The prepared solution may be stored for up to 24 hours at a temperature of 2°C to 8°C. From a microbiological standpoint, the prepared solution should be used immediately. Otherwise, responsibility for the time and storage conditions of the prepared solution lies with the user.
Pharmaceutical incompatibilities
The solution has a low pH and may be physically or chemically unstable when mixed with other substances. Vancomycin solutions should not be mixed with other solutions except those whose compatibility has been reliably confirmed.
Mixing vancomycin with alkaline solutions should be avoided.
Simultaneous administration and mixing of vancomycin solutions with chloramphenicol, corticosteroids, methicillin, heparin, aminophylline, cephalosporin antibiotics, and phenobarbital are not recommended.
Overdose
In case of overdose, effects resulting from high serum vancomycin concentrations (ototoxic and nephrotoxic effects) may be expected.
Supportive treatment maintaining glomerular filtration is recommended. Vancomycin is only minimally removed from blood by hemodialysis or peritoneal dialysis. Limited benefit has been reported from hemofiltration using Amberlite XAD-4 resin.
Other sources of information
Medical advice/education
Antibiotics are used to treat bacterial infections. They are ineffective against viral infections.
If a physician has prescribed antibiotics for a patient, they are necessary for treating a specific, current illness.
Despite antibiotic use, some bacteria may survive or continue to multiply. This phenomenon is called resistance; it causes antibiotic treatment to sometimes be ineffective.
Improper use of antibiotics promotes the development of resistance. Patients can also facilitate the emergence of resistance and thereby delay recovery or reduce the effectiveness of antibiotic therapy if they do not adhere to proper:

• dosing,
• treatment schedule,
• duration of treatment.

Therefore, to preserve the effectiveness of this medicine, it is essential to:
1 – use antibiotics only when prescribed by a physician
2 – strictly follow the prescribed method of administration
3 – not reuse an antibiotic without a physician's recommendation, even to treat a similar illness.