Vancomycin neupharm

PACKAGE LEAFLET: INFORMATION FOR THE USER

Warning! Keep the leaflet, information on the immediate packaging in a foreign language!
Vancomycin Neupharm (Vancomicina Azevedos) , 1 g
powder for preparation of concentrate for infusion solution
Vancomycinum
Vancomycin Neupharm and Vancomicina Azevedos are different trade names of the same medicine.
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet for future reference.
• 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.

Leaflet contents

1. What Vancomycin Neupharm is and what it is 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 pack and other information

1. What Vancomycin Neupharm 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 used in all age groups by infusion (intravenous drip) to treat the following serious infections:

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

Vancomycin may be administered orally in adults and children for the treatment of infection of the mucous membrane of the small and large intestine associated with mucosal damage (pseudomembranous colitis) caused by Clostridium difficile bacteria.

2. Important information before using Vancomycin Neupharm

When not to use Vancomycin Neupharm

• 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 Neupharm, 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 disorders, especially if elderly (hearing tests may be required during treatment);
• the patient has impaired kidney function (blood tests and monitoring of liver and kidney function may be necessary during treatment);
• the patient is receiving vancomycin by infusion to treat Clostridium difficile-associated diarrhoea instead of oral administration;
• the patient has ever experienced severe skin rash, skin peeling, blisters, and/or oral mucosal ulcers after receiving vancomycin.

Severe 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 Neupharm, discuss with the doctor, hospital pharmacist, or nurse if:

• the patient is receiving vancomycin treatment for a prolonged period (blood tests and monitoring of liver and kidney function may be required during treatment);
• the patient develops any skin reaction during treatment;
• the patient develops severe or persistent diarrhoea during or after completion of vancomycin treatment; in such a case, immediate medical consultation is necessary. This may be a sign of intestinal inflammation (pseudomembranous colitis), which can 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 anaesthetic agents in children has been associated with skin flushing (red man syndrome) and allergic reactions. Additionally, concomitant use with other drugs such as aminoglycoside antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs, e.g. ibuprofen), or amphotericin B (used in fungal infections) may increase the risk of kidney damage, necessitating more frequent blood and kidney function tests.

Vancomycin Neupharm and other medicines
Inform the doctor, pharmacist, or nurse about all medicines currently used, recently used, or planned to be used by the patient.
Exercise particular caution if the patient is taking other medicines that may interact with vancomycin, for example:

• Concomitant use of vancomycin and anaesthetic agents may cause hypotension, dyspnoea, skin flushing, urticaria, and pruritus; it may also cause a severe reaction resembling an allergic reaction. The incidence of these reactions is reduced when vancomycin is administered by slow intravenous infusion prior to anaesthetic administration.
• When vancomycin is used concomitantly with drugs that may impair 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.
• Special caution is required 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 benefit outweighs the risk. The doctor may recommend monitoring serum vancomycin levels to reduce the risk of fetal toxicity.
Vancomycin passes into human milk and therefore may be used during breastfeeding only if other antibiotics have proven ineffective. If vancomycin treatment in the mother is absolutely necessary, the doctor will carefully monitor the infant or may recommend discontinuation of breastfeeding.
There are no data on the effects on fertility.

Driving and operating machinery
Vancomycin Neupharm has negligible influence on the ability to drive and use machines.

3. How to use Vancomycin Neupharm

The patient will receive Vancomycin Neupharm 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,
• the patient's hearing status,
• any other medications the patient is taking.

Intravenous administration
Adults and adolescents (aged 12 years and older)
The dose will be determined based on the patient's body weight. The usual dose administered by infusion is 15 to 20 mg per kilogram 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 kilogram 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
The dose will be determined based on the patient's body weight. The usual dose administered by infusion is 10 to 15 mg per kilogram 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 some 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 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 given every 6 hours. The maximum daily dose should not exceed 2 g.

Method of administration
Intravenous infusion (drip) means that the medicine flows from an infusion bottle or 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 the vein over at least 60 minutes.

When used to treat gastrointestinal disorders (e.g., pseudomembranous colitis), the medicine must be given orally as an oral solution (the patient will take the medicine by mouth).

Instructions for preparing the solution prior to administration are provided in the section "Information for healthcare professionals only" 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, the patient may undergo blood tests and urine analysis, and may also have hearing tests to monitor for potential adverse effects.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Vancomycin may cause allergic reactions; however, 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 notified immediately.
If the patient notices any of the following symptoms, vancomycin should be discontinued and medical advice should be sought immediately:

• Red, flat, target-like or circular spots on the trunk, often with blisters in the center, skin peeling, and ulcers in the mouth, throat, nose, genital area, 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 body temperature, 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 airflow in the upper respiratory tract)
• Rash and inflammation of the mucous membranes of the mouth, itching, itchy rash, urticaria
• Kidney function disturbances, usually detected in blood tests
• Redness of the upper body and face, phlebitis (inflammation of the vein)

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 white blood cells, red blood cells, and platelets (blood cells responsible for blood clotting)
• Increase in certain white blood cells in the blood
• Balance disorders, tinnitus, dizziness
• Vasculitis (inflammation of blood vessels)
• 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 diarrhea, which may contain blood

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

• Vomiting, diarrhea
• Confusion, drowsiness, lack of energy, swelling, fluid retention, reduced urine output
• Rash with swelling and pain behind the ears, neck, groin, under the chin, and under the arms (swelling of lymph nodes), abnormal blood test results and liver function tests
• Rash with blisters and fever

Reporting of adverse reactions
If any adverse reactions occur, including any 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 at 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 this medicine.

5. How to store Vancomycin Neupharm

• Keep this medicine out of sight and reach of children.
• Do not use after the expiry date stated on the outer packaging after EXP/VAL and on the immediate packaging after VAL.
• The expiry date refers to the last day of the stated month.
• Store below 25°C.
• Store in the original packaging.
• Storage of solutions: see "Preparation of infusion solution" at the end of this leaflet, in the section intended for medical personnel.
• Medicines must not be disposed of via wastewater 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 Neupharm contains
The active substance 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 pack
Vancomycin Neupharm is a white or slightly brownish powder, placed in a vial made of colourless
type I glass, with a rubber stopper and aluminium cap, packed in a cardboard box.
The pack contains 10 vials.

For more detailed information, please contact the marketing authorisation holder or the parallel importer.

Marketing authorisation holder 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:
Neupharm Sp. z o.o.
ul. Ługowa 85
96-320 Mszczonów
Poland

Repackaged by:
LABOR Przedsiębiorstwo Farmaceutyczno-Chemiczne Sp. z o.o.
ul. Długosza 49
51-162 Wrocław
Poland

GP LABEL Ostrowski spółka jawna
ul. Obywatelska 128/152
94-104 Łódź
Poland

Marketing authorisation number in Portugal, country of export: 5623749
Parallel import authorisation number: 340/24

Information intended exclusively for healthcare professionals:

The medicinal product should be administered by intravenous infusion or orally. It must not be given as an 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, aiming to achieve 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 higher than 2 g per single 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 newborns (from birth up to 27 days postnatal age) and preterm newborns (from birth up to expected date of delivery plus 27 days)
To determine the appropriate dosing regimen for newborns, advice should be sought from a physician experienced in treating neonates. One possible vancomycin dosing regimen for newborns is presented in the table below:

PMA: post-conceptional 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 the case of prosthetic joint infections, prolonged cycles of oral suppressive therapy with appropriate antibiotics should be considered.
*** The duration and need for combination therapy depend on the type of prosthesis and microorganism.
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 concentration monitoring of vancomycin, rather than relying on a fixed dosing schedule—especially in patients with severe renal impairment or those undergoing renal replacement therapy—due to multiple variable factors affecting 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, prolonging the dosing interval is preferred over administering smaller doses.
Concomitant administration of other 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 essentially 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 concentration (mg/dL)]
Women: 0.85 × the value calculated by the formula above
The usual initial dose for 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 below 20 mL/min) or those undergoing renal replacement therapy, appropriate dosing intervals and subsequent dose sizes 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, consideration may be given to withholding the next dose until vancomycin serum concentration measurements 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 concentration (mg/dL)
eGFR (mL/min/1.73 m²) = (height in cm × 36.2) / serum creatinine concentration (μmol/L)
For neonates and infants under 1 year of age, expert consultation should be sought, as the Schwartz formula is not applicable in these patients.
The dosing recommendations for children and adolescents provided in the table below follow the same principles as those for adult patients.

* Appropriate dosing intervals and subsequent dose sizes largely depend on
the RRT method used and should be determined based on serum vancomycin concentrations prior to dosing
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 higher 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,
similarly 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 clinical course of the disease
may be necessary. Whenever possible, the antibacterial agent suspected of causing CDI should be discontinued.
Appropriate fluid and electrolyte replacement should be ensured.
Monitoring serum vancomycin concentration
The frequency of therapeutic drug monitoring should be individually tailored 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,
serum 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 serum 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; dosing recommendations
provided in this section for the intravenous route refer to this method
of administration.
Vancomycin should be administered exclusively via 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 200 mL per 1 g).
Patients with restricted fluid intake may receive a 1 g/100 mL solution, but with this higher concentration,
the risk of infusion-related adverse reactions increases.
Continuous vancomycin infusion may be considered, e.g., in patients with unstable vancomycin clearance.
Oral administration
The vial contents may be used to prepare an oral solution. The oral solution is prepared by dissolving
the contents of one vial (1000 mg vancomycin) in 30 mL of water. The appropriate dose can be administered
to the patient orally or via a nasogastric tube. Syrup may be added to the solution to improve taste.
Preparation of infusion solution
Dissolve the contents of the vial in 20 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.
Intermittent 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
slowly intravenously, at a maximum rate of 10 mg/min, over at least 60 minutes.
Continuous infusion
Should only be used when intermittent infusions are not feasible. The 50 mg/mL vancomycin solution should be diluted
in an appropriate volume of 5% glucose solution or 0.9% sodium chloride solution so 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,
the responsibility for the time and conditions of storage 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.
Vancomycin should be avoided with alkaline solutions.
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.
Inappropriate use of antibiotics promotes the development of resistance. Patients can also contribute
to the development of resistance and thereby delay recovery or reduce the effectiveness of antibiotic therapy
by failing to 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 antibiotics without a physician's recommendation, even to treat a similar illness.