Edicin

Package leaflet: Information for the patient

Edicin, 500 mg, powder for solution for infusion
Edicin, 1 g, powder for solution for infusion
Vancomycinum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Leaflet contents:

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

1. What Edicin is and what it is used for

Vancomycin is an antibiotic belonging to the glycopeptide class of antibiotics. Vancomycin acts by killing certain bacteria that cause infections. Vancomycin in powder form is used to prepare a solution for infusion or an oral solution. Vancomycin is used in all age groups as an infusion (intravenous drip) 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 at-risk patients undergoing major surgical procedures;
central nervous system infections;
bloodstream infections associated with the above-mentioned infections.
Oral vancomycin may be administered to adults and children for the treatment of infection of the mucosa of the small and large intestine associated with mucosal damage (pseudomembranous colitis) caused by Clostridium difficile bacteria.

2. Information before using Edicin

When not to use Edicin
if the patient is allergic to vancomycin.

Warnings and precautions
Severe adverse reactions, potentially leading to loss of vision, have occurred when vancomycin has been injected into the eye.

Before starting treatment with Edicin, discuss with your doctor, hospital pharmacist, or nurse if:

• the patient has previously experienced an allergic reaction to teicoplanin, as this may indicate allergy to vancomycin as well;
• the patient has hearing problems, especially if elderly (hearing tests may be necessary during treatment);
• the patient has impaired kidney function (blood tests and monitoring of liver and kidney function may be required during treatment);
• the patient is receiving vancomycin by intravenous infusion for the treatment of Clostridium difficile-associated diarrhoea instead of oral administration;
• the patient has ever developed severe skin rash, skin peeling, blisters, and/or oral mucosal ulcers after receiving vancomycin;
• patients receiving Edicin have experienced symptoms of allergic reactions, including difficulty breathing and chest pain. If any of these symptoms occur, Edicin must be discontinued immediately and the doctor or emergency medical services should be contacted.

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 treatment must be stopped immediately and medical advice sought without delay.

During treatment with Edicin, discuss with your doctor, hospital pharmacist, or nurse if:

• the patient is receiving long-term vancomycin therapy (blood tests and monitoring of liver and kidney function may be necessary during treatment);
• the patient develops any skin reaction during treatment;
• the patient develops severe or prolonged diarrhoea during or after vancomycin treatment; in such cases, immediate medical consultation is required. This may be a sign of intestinal inflammation (pseudomembranous colitis), which can occur during antibiotic therapy.

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 to monitor vancomycin blood levels may be necessary.

Concomitant administration of vancomycin and anaesthetic agents in children has been associated with skin flushing (red man syndrome) and allergic reactions. Additionally, concurrent use with other drugs such as aminoglycoside antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs, e.g. ibuprofen), or amphotericin B (an antifungal agent) may increase the risk of kidney damage, thus more frequent blood tests and kidney function monitoring may be required.

Edicin and other medicines
Tell your doctor, pharmacist, or nurse about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

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, shortness of breath, skin flushing, urticaria, and itching; it may also cause a strong reaction resembling an allergic reaction. The incidence of these reactions is lower when vancomycin is administered by slow intravenous infusion before the anaesthetic agent.
• 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 fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning a pregnancy, she should consult her 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 foetal toxicity.

Vancomycin passes into human milk; therefore, it 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 studies on the effect on fertility.

Driving and operating machinery
Edicin has negligible influence on the ability to drive and operate machinery.

3. How to use Edicin

The patient will receive Edicin administered by medical personnel during hospitalization.
The doctor will decide the daily dose of the medicine the patient should receive 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,
• 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 infusion dose is 15 to 20 mg per kg of body weight. This dose is usually administered 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 dose of vancomycin must not exceed 2 g per dose.
Use in children
Children from one month of age and children under 12 years of age
The dosage will be determined based on the patient's body weight. The usual infusion dose is 10 to 15 mg per kilogram of body weight. This dose is usually administered every 6 hours.
Preterm infants and full-term newborns (0 to 27 days)
The dose will be calculated based on gestational age [the time elapsed from the first day of the mother's last menstrual period to delivery (gestational age) plus the time elapsed since the child's birth (postnatal age)].
For 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 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 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 intravenously over at least 60 minutes.
When used to treat gastrointestinal disorders (so-called pseudomembranous colitis), the medicine must be given as an oral solution (the patient will take the medicine orally).
Instructions for preparing the solution before 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 analysis 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, 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, peeling of the skin, 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").
• Chest pain, which may be a symptom of a potentially serious allergic reaction known as Kounis syndrome.

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

• Decreased blood pressure
• Shortness of breath, wheezing (a high-pitched sound caused by an obstruction in the upper airways)
• Rash and inflammation of the mucous membranes of the mouth, itching, itchy rash, urticaria
• Kidney function disorders usually detected in blood tests
• Redness of the upper body and face, phlebitis (inflammation of a vein)
• Increased liver enzyme activity

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):

• Decreased number of white blood cells, red blood cells, and platelets (blood cells responsible for blood clotting)
• Increased number of 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 a severe skin allergic reaction involving skin peeling or blister formation. This may be accompanied by high fever and joint pain.
• Cardiac arrest
• Intestinal inflammation causing abdominal pain and diarrhoea, which may contain blood.

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

• Vomiting, diarrhoea
• Confusion, 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
• Excessive breakdown of red blood cells, leading to fatigue and pale skin (haemolytic anaemia)

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
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Edicin

Keep this medicine out of the sight and reach of children.
Do not use after the expiry date stated on the packaging after EXP.
The expiry date refers to the last day of the stated month.
Store below 25 °C.
Keep 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 should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Edicin contains
The active substance is vancomycin. Each vial contains 500 mg or 1 g of vancomycin.
Edicin does not contain any other ingredients.

What Edicin looks like and contents of the pack
Edicin is a white or almost white lyophilized powder, placed in a clear glass vial with a stopper and an aluminium seal, packed in a cardboard box.
The pack contains 1 or 10 vials.

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
A-6250 Kundl, Austria

Manufacturer
Lek Pharmaceuticals d.d
Verovškova 57
1526 Ljubljana, Slovenia

For further information regarding this medicinal product, please contact:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50 C
02-672 Warszawa
tel. +48 22 209 70 00
(logo of the marketing authorisation holder)

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 injection (bolus) or by intramuscular route (see section 4.8 of the Summary of Product Characteristics).

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 attainment of the target 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 to 27 days postnatal age) and preterm newborns (from birth 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 of the possible vancomycin dosing regimens for newborns is presented in the table below (see SmPC section 4.4):

PMA: post-conceptional age [time elapsed from the first day of the last menstrual period to birth (gestational age) plus time elapsed from 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, longer cycles of oral suppressive therapy with appropriate antibiotics should be considered.
*** The duration and need for combination therapy depend on the type of valve and 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 those 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 interval between doses 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 (see SmPC section 4.4).

Vancomycin is poorly removed by intermittent hemodialysis. However, the use of high-permeability 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 × the value calculated for men

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 < 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 (see SmPC section 4.4). Depending on the clinical situation, withholding the next dose until vancomycin serum concentration is measured may be considered.

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 does not apply to these patients.

The 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 applied RRT method and should be established based on vancomycin serum concentrations
before administration and residual renal function. Depending on the clinical situation, consideration
may be given to withholding the next dose until vancomycin blood 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
vancomycin serum concentrations (see SmPC section 4.6).
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 with vancomycin
125 mg four times daily for 10 days may be considered, followed by 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. Adequate fluid and electrolyte replacement should be ensured.
Monitoring vancomycin serum concentrations
The frequency of monitoring therapeutic drug levels should be individually tailored to the clinical situation and response to treatment; sampling frequency may range from daily 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 (see SmPC section 4.4).
Therapeutic minimum blood concentrations of vancomycin 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, providing better coverage of organisms classified as susceptible with an MIC ≥1 mg/l (see SmPC sections 4.4 and 5.1).
In predicting individual dosing required to achieve appropriate AUC values, 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 (see SmPC section 5.1).
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 only by 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 or at least 200 ml per 1000 mg), see SmPC section 4.4.
Patients with restricted fluid intake may receive a 500 mg/50 ml (1000 mg/100 ml) solution, but with this higher concentration, the risk of infusion-related adverse reactions is increased.
Continuous vancomycin infusion 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 one 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 improve taste.
Preparation of infusion solution
Edicin 500 mg
Dissolve the contents of the vial in 10 ml of water for injections.
Edicin 1 g
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 100 ml or 200 ml of 5% glucose solution or 0.9% sodium chloride solution. The vancomycin concentration in the final 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
Use only 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 storage time and 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 vancomycin serum concentrations (ototoxic and nephrotoxic effects) may be expected.
Symptomatic treatment maintaining glomerular filtration is recommended. Vancomycin is only minimally removed from 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 a doctor 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 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, the following should be observed:
1 – use antibiotics only when prescribed by a doctor
2 – strictly follow the prescribed method of administration
3 – do not reuse antibiotics without a doctor's recommendation, even to treat a similar illness.