Vancomicin Neupharm

LEAFLET INCLUDED IN THE PACKAGING: INFORMATION FOR THE USER

Warning! Keep the leaflet, the information on the immediate packaging is in a foreign language!

Vancomycin Neupharm(Vancomycin Azevedos) , 1 g
powder for concentrate for solution for infusion
Vancomycinum
Vancomycin Neupharm and Vancomycin Azevedos are different trade names for the same medicine.

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor, pharmacist or nurse.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Vancomycin Neupharm and what is it used for
• 2. Important information before using Vancomycin Neupharm
• 3. How to use Vancomycin Neupharm
• 4. Possible side effects
• 5. How to store Vancomycin Neupharm
• 6. Contents of the packaging and other information

1. What is Vancomycin Neupharm 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 concentrate for solution for infusion or oral solution. Vancomycin is used in all age groups in the form of an infusion (drip) to treat the following severe 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 patients at risk undergoing major surgical procedures;
• infections of the central nervous system;
• blood infections related to the above infections.

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

2. Important information before using Vancomycin Neupharm

When not to use Vancomycin Neupharm

• if the patient is allergic to vancomycin.

Warnings and precautions

After injecting vancomycin into the eye, severe side effects have occurred, which can lead to loss of vision. Before starting treatment with Vancomycin Neupharm, you should discuss this with your doctor, hospital pharmacist or nurse if:

• the patient has previously had an allergic reaction to teicoplanin, as this may mean 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 liver and kidney function tests may be necessary during treatment);
• the patient is receiving vancomycin by infusion to treat diarrhea associated with Clostridium difficileinfection, instead of oral administration;
• the patient has ever had a severe skin rash or skin peeling 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 see a doctor immediately. During treatment with Vancomycin Neupharm, you should discuss this with your doctor, hospital pharmacist or nurse if:

• the patient is receiving vancomycin treatment for a long time (blood tests and liver and kidney 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, they should consult a 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 vancomycin accumulation in the blood. In this age group, blood tests may be necessary to monitor vancomycin levels in the blood. Concurrent administration of vancomycin and anesthetics in children is associated with the occurrence of skin redness and allergic reactions. Additionally, concurrent use with other medications, such as aminoglycoside antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen) or amphotericin B (a medication used to treat fungal infections), may increase the risk of kidney damage, and therefore, more frequent blood tests and kidney function tests may be necessary.

Vancomycin Neupharm and other medicines

You should tell your doctor, pharmacist or nurse about all medicines that the patient is currently taking or has recently taken, as well as any medicines that the patient plans to take. You should be especially careful if the patient is taking other medicines that may interact with vancomycin, such as:

• Concurrent use of vancomycin and anesthetics may cause low blood pressure, shortness of breath, skin redness, hives, and itching; it may also cause a severe reaction resembling an allergic reaction. The frequency of these disorders is lower when vancomycin is administered by slow intravenous infusion before anesthesia.
• When using medications that can damage hearing, nerves, and/or kidneys (such as ethacrynic acid, aminoglycoside antibiotics, amphotericin B, bacitracin, polymyxin B, piperacillin/tazobactam, colistin, viomycin or cisplatin), the doctor will carefully monitor the patient's condition.
• When using vancomycin and muscle relaxants, the doctor will exercise special caution.

Pregnancy, breastfeeding and fertility

If the patient is pregnant or breastfeeding, thinks they may be pregnant or are planning to have a baby, they should consult their doctor before using this medicine. Vancomycin can be used during pregnancy only if absolutely necessary, when the doctor believes that the benefits of treatment outweigh the risks. The doctor will recommend monitoring vancomycin levels in the blood to minimize the risk of toxic effects on the fetus. Vancomycin passes into breast milk, and therefore, it can be used during breastfeeding only if other antibiotics have been ineffective. If the mother's treatment with vancomycin is absolutely necessary, the doctor will carefully monitor the condition of the infant or recommend stopping breastfeeding. There are no fertility studies.

Driving and using machines

Vancomycin Neupharm has a negligible effect on the ability to drive and use machines.

3. How to use Vancomycin Neupharm

The patient will receive Vancomycin Neupharm 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 dose administered will depend on:

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

Intravenous administration

Adults and adolescents (12 years and older)

The dose will be determined based on the patient's body weight. The usual dose for infusion is 15 to 20 mg/kg 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 up to 30 mg/kg of body weight. The maximum daily dose of vancomycin should not exceed 2 g.

Use in children

Children from the first month of life and children under 12 years of age The dose will be determined based on the patient's body weight. The usual dose for infusion is 10 to 15 mg/kg of body weight. This dose is usually administered every 6 hours. Premature infants and full-term newborns (from birth to 27 days of postnatal age) The dose will be calculated based on postmenstrual age [the time from the first day of the last menstrual period to birth (gestational age) plus the time from birth (postnatal age)].

Administration method

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. If used to treat gastrointestinal disorders (so-called pseudomembranous colitis), the medicine must be administered orally (the patient will take the medicine by mouth). Instructions for preparing the solution before administration can be found in "Information intended for healthcare professionals only" at the end of the leaflet.

Duration of treatment

The duration of treatment depends on the type of infection in the patient and may last for several weeks. The duration of treatment may vary depending on the patient's response to treatment. During treatment, the patient may have blood tests and urine analysis, and may also have a hearing test to check for potential side effects. If the patient has any further doubts about using this medicine, they should consult their doctor, pharmacist or nurse.

4. Possible side effects

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

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 attending doctor.

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

• red, flat, target-like or round patches on the torso, often with blisters in the center, skin peeling, mouth ulcers, throat, nose, genital and eye ulcers. 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 hypersensitivity syndrome).
• red, peeling rash with nodules under the skin and blisters with fever at the beginning of treatment (acute generalized exanthematous pustulosis, see section 2 "Warnings and precautions").

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

• low blood pressure
• shortness of breath, wheezing (high-pitched sound caused by an obstruction in the airway)
• rash and inflammation of the mucous membrane of the mouth, itching, itchy rash, hives
• kidney problems detected 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
• vasculitis
• 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 skin peeling or blistering. This may be accompanied by high fever and joint pain.
• cardiac arrest
• intestinal inflammation 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 this leaflet, the patient should tell their doctor, pharmacist or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring 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. By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Vancomycin Neupharm

• The medicine should be stored out of sight and reach of children.
• Do not use after the expiry date stated on the outer packaging after the words EXP/VAL and on the immediate packaging after VAL.
• The expiry date refers to the last day of the month stated.
• Store at a temperature below 25°C.
• Store in the original packaging.
• Storage of solutions: see "Preparation of the solution for infusion" at the end of the leaflet, in the section intended for healthcare professionals.
• 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 Vancomycin Neupharm contains

The active substance of the medicine is vancomycin. Each vial contains 1 g of vancomycin in the form of vancomycin hydrochloride. Vancomycin Neupharm does not contain any other ingredients.

What Vancomycin Neupharm looks like and contents of the packaging

Vancomycin Neupharm is a white or slightly brown powder, placed in a vial made of colorless glass type I, with a rubber stopper and an aluminum cap, in a cardboard box. The packaging contains 10 vials. For more detailed information, please contact the marketing authorization holder or parallel importer.

Marketing authorization holder in Portugal, the 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:

Neupharm Sp. z o.o. ul. Ługowa 85 96-320 Mszczonów

Repackaged by:

LABOR Przedsiębiorstwo Farmaceutyczno-Chemiczne Sp. z o.o. ul. Długosza 49 51-162 Wrocław GP LABEL Ostrowski spółka jawna ul. Obywatelska 128/152 94-104 Łódź Portuguese marketing authorization number:5623749

Parallel import authorization number: 340/24

Date of leaflet approval: 18.09.2024

[Information about the trademark]

Information intended for healthcare professionals only:

The medicinal product should be administered by intravenous infusion or orally. It should not be administered by rapid intravenous injection (bolus) or intramuscularly. Intravenous administrationThe initial dose should be determined based on total body weight. Subsequent dose adjustments should be based on serum vancomycin levels, with the aim of achieving the target therapeutic level. When determining subsequent doses and intervals, kidney function should also be taken into account. Recommended dosing regimens are as follows: Patients 12 years and olderThe recommended dose is 15 to 20 mg/kg every 8 to 12 hours (do not exceed 2 g per dose). In critically ill patients, a loading dose of 25-30 mg/kg may be used to rapidly achieve the target minimum vancomycin level in the blood. Infants from the first month of life and children under 12 years of ageThe recommended intravenous dose is 10 to 15 mg/kg every 6 hours. Full-term newborns (from birth to 27 days of postnatal age) and premature infants (from birth to the expected date of delivery plus 27 days)To determine the dosing regimen for newborns, consult a doctor experienced in treating newborns. One possible vancomycin dosing regimen for newborns is presented in the table below: PMA: postmenstrual age [time from the first day of the last menstrual period to birth (gestational age) plus the time from birth (postnatal age)]. Duration of treatmentThe recommended duration of treatment is presented in the table below. In each case, the duration of treatment should be adjusted according to the type and severity of the infection and the individual clinical response. The duration of treatment may be variable, depending on the individual patient's response to treatment.

* 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 to 72 hours. ** In the case of prosthetic joint infections, consider longer cycles of oral suppressive therapy with appropriate antibiotics. *** The duration and need for combination therapy depend on the type of valve and microorganism. Adult patientsDose adjustments 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 level (mg/dl) Women: 0.85 x the value calculated using the above formula The 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 kidney problems (creatinine clearance below 20 ml/min) or patients undergoing renal replacement therapy, the appropriate dosing intervals and subsequent doses depend largely on the RRT method used and should be determined based on serum vancomycin levels and residual renal function. Depending on the clinical situation, it may be considered to withhold the next dose until the vancomycin level in the blood is determined. In critically ill patients with kidney problems, the initial loading dose (25 to 30 mg/kg) should not be reduced. Children and adolescentsDose adjustments in children aged 1 year and older and adolescents may be based on the estimated glomerular filtration rate (eGFR) using the modified Schwartz formula: eGFR (ml/min/1.73 m^2) = (height in cm x 0.413) / serum creatinine level (mg/dl) eGFR (ml/min/1.73 m^2) = (height in cm x 36.2 / serum creatinine level (μmol/l) For newborns and infants under 1 year of age, consult an expert, as the Schwartz formula does not apply to such patients. The approximate dosing recommendations for children and adolescents presented in the table below are subject to the same rules as the recommendations for adult patients.

* Appropriate dosing intervals and subsequent doses depend largely on the RRT method used and should be determined based on serum vancomycin levels and residual renal function. Depending on the clinical situation, it may be considered to withhold the next dose until the vancomycin level in the blood is determined. Patients with liver problemsThere is no need to adjust the dose in patients with liver failure. PregnancyIn pregnant women, it may be necessary to significantly increase the doses to achieve therapeutic vancomycin levels in the blood. Obese patientsIn obese patients, the initial dose should be adjusted individually based on total body weight, just like in patients with normal body weight.

Oral administration

Patients 12 years and olderTreatment of Clostridium difficile-associated infections (CDI) For the first episode of non-severe CDI, the recommended vancomycin dose is 125 mg every 6 hours for 10 days. The 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. For multiple recurrences, treatment of the current CDI episode with vancomycin 125 mg four times a day for 10 days, followed by a gradual decrease in dose to 125 mg per day or a pulsing regimen (125-500 mg/day every 2-3 days) for at least 3 weeks may be considered. Newborns, infants and children under 12 years of ageThe recommended vancomycin dose 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 offending antibiotic should be discontinued. Adequate fluid and electrolyte supplementation should be ensured. Monitoring vancomycin levels in the blood The frequency of monitoring therapeutic drug levels 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 at least once a week in stable patients with a visible response to treatment. In patients undergoing intermittent hemodialysis, vancomycin levels should be determined before the start of the hemodialysis session. Monitoring vancomycin levels in the blood after oral administration should be performed in patients with inflammatory bowel disease. The minimum therapeutic vancomycin level in the blood should be 10-20 mg/l, depending on the site of infection and pathogen susceptibility. Clinical laboratories usually recommend a minimum level 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 initial individual dose and when modifying doses based on TDM results. Administration method Intravenous administrationVancomycin is usually administered intravenously in the form of intermittent infusions; the dosing recommendations presented in this section for the intravenous route refer to this method of administration. Vancomycin should be administered only by slow intravenous infusion lasting at least 1 hour or at a maximum rate of 10 mg/min (longer period) in a sufficiently diluted solution (at least 200 ml per 1 g). Patients with limited fluid intake may receive a solution of 1 g/100 ml, but at this higher concentration, the risk of infusion-related adverse reactions is increased. Continuous infusion of vancomycin may be considered, e.g., in patients with unstable vancomycin clearance. Oral administrationThe contents of the vial can be used to prepare an oral solution. The oral solution is prepared by dissolving the contents of the vial (1000 mg of vancomycin) in 30 ml of water. The appropriate dose can be administered to the patient to drink or through a nasogastric tube. Syrup can be added to the solution to improve the taste. Preparation of the solution for infusionThe contents of the vial should be dissolved in 20 ml of water for injection. 1 ml of the resulting solution contains 50 mg of vancomycin. The solution can be further diluted depending on the administration method. Multiple infusions The prepared solution should be diluted in 200 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 intravenously slowly, at a maximum rate of 10 mg/min, over at least 60 minutes. Continuous infusion It should be used only when multiple infusions are not possible. The vancomycin solution with a concentration of 50 mg/ml should be diluted in a sufficient volume of 5% glucose solution or 0.9% sodium chloride solution so that the patient receives the prescribed daily dose in a drip infusion over 24 hours. Stability and storage conditions of solutionsThe prepared solution can be stored for up to 24 hours at a temperature of 2°C to 8°C. For microbiological reasons, the prepared solution should be used immediately. Otherwise, the user is responsible for the storage time and conditions of the prepared solution. IncompatibilitiesThe 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 for those whose compatibility has been reliably verified. Mixing vancomycin with alkaline solutions should be avoided. It is not recommended to use vancomycin solutions concurrently with or mix them with chloramphenicol, corticosteroids, methicillin, heparin, aminophylline, cephalosporin antibiotics, or phenobarbital. OverdoseIn case of overdose, effects due to high vancomycin levels in the blood (ototoxic and nephrotoxic effects) can be expected. Supportive treatment maintaining renal function is recommended. Vancomycin is poorly removed from the blood by hemodialysis or peritoneal dialysis. Limited benefit has been reported with the use of 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 the doctor has prescribed antibiotics for the patient, they are necessary to treat the current disease. Despite antibiotic treatment, some bacteria may survive or continue to 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.

Therefore, to maintain the effectiveness of this medicine, you should:

• 1 - use antibiotics only when prescribed by a doctor

• 2 - strictly follow the prescribed method of use
• 3 - do not use antibiotics again without the doctor's recommendation, even to treat a similar disease.