Vancomycin aptapharma

Package leaflet: information for the patient

Vancomycin AptaPharma, 500 mg, powder for preparation of concentrate solution for infusion
Vancomycin AptaPharma, 1000 mg, powder for preparation of concentrate solution for infusion
Vancomycini hydrochloridum
Please read carefully the entire leaflet before use, 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 of the leaflet:

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

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

Vancomycin is an antibiotic belonging to a class of antibiotics known as "glycopeptides". Vancomycin works by killing certain bacteria that cause infections.
Vancomycin is administered intravenously in all age groups for the treatment of the following serious infections:
skin and soft tissue infections;
bone and joint infections;
lung infection known as "pneumonia";
hospital-acquired pneumonia, including ventilator-associated pneumonia;
infection of the inner lining of the heart (endocarditis), and prevention of endocarditis in high-risk patients undergoing major surgical procedures.
Oral vancomycin may be used 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.
Vancomycin powder is used to prepare an infusion solution or an oral solution.

2. Important information before using Vancomycin AptaPharma

When not to use Vancomycin AptaPharma
if the patient is allergic to vancomycin
intramuscularly due to the risk of necrosis at the injection site.

Warnings and precautions
Before starting treatment with Vancomycin AptaPharma, discuss with your doctor, hospital pharmacist, or nurse if:

• the patient has ever had severe skin rash, skin peeling, blisters, and/or oral mucosal ulcers after receiving vancomycin;
• the patient previously had an allergic reaction to teicoplanin, as this may indicate that
  the patient is also allergic to vancomycin;
• the patient has hearing problems, especially if 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 diarrhea associated with Clostridium difficile infection, instead of oral administration.

Severe skin reactions have been reported during 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 experiences any of the symptoms described in section 4, vancomycin must be discontinued immediately and medical advice must be sought without delay.

During vancomycin treatment, consult your doctor, hospital pharmacist, or nurse if:

• the patient is receiving vancomycin for a prolonged period (blood tests and monitoring of liver and kidney function may be necessary);
• the patient is over 65 years of age (the doctor may need to adjust the dose);
• the patient develops any skin reaction during treatment;
• the patient develops severe or persistent diarrhea during or after completion of vancomycin treatment; in such case, immediate medical consultation is required. This may be a sign of intestinal inflammation (pseudomembranous colitis), which can occur during antibiotic therapy.

Severe adverse reactions, potentially leading to vision loss, have occurred following intravitreal injection of vancomycin.

Patients receiving Vancomycin AptaPharma have experienced symptoms of allergic reactions, including difficulty breathing and chest pain. If the patient experiences any of these symptoms, administration of Vancomycin AptaPharma must be stopped immediately and the patient should contact a doctor or emergency medical services.

Children
Vancomycin should be used with particular caution in premature infants and young infants, 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 required to monitor vancomycin blood levels.

Vancomycin AptaPharma and other medicines
Inform your doctor, pharmacist, or nurse about all medicines currently or recently taken, as well as any medicines the patient intends to take. Additionally, do not take any new medicines without consulting a doctor.

The following medicines may interact with vancomycin when used concomitantly, for example, drugs used in the treatment of:

• bacterial infections (streptomycin, neomycin, gentamicin, kanamycin, amikacin, bacitracin, tobramycin, polymyxin B, colistin),
• tuberculosis (viomycin),
• fungal infections (amphotericin B),
• cancer (cisplatin), and
• drugs used to relax muscles during anesthesia,
• anesthetics (if the patient is to undergo general anesthesia),
• proton pump inhibitors,
• drugs that inhibit intestinal motility (medicines used to relieve diarrhea symptoms),
• diuretics (medicines for fluid retention),
• non-steroidal anti-inflammatory drugs (medicines used to treat inflammation, mild to moderate pain, and fever).

If vancomycin is administered at the same time as other medicines, the doctor may order blood tests to adjust its dose.

Concomitant administration of vancomycin and anesthetic agents in children has been associated with skin redness (flushing) and allergic reactions. Similarly, concomitant use with other drugs such as aminoglycoside antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen), or amphotericin B (a drug used in fungal infections), or piperacillin with tazobactam (in case of parenteral formulations), may increase the risk of kidney damage; therefore, more frequent blood tests and kidney function monitoring may be required.

Pregnancy and breastfeeding
Pregnancy
If the patient is pregnant, suspects she may be pregnant, or is planning a pregnancy, she should consult her doctor before using this medicine. Vancomycin AptaPharma may be administered during pregnancy and breastfeeding only if absolutely necessary. The doctor will decide whether the patient should receive Vancomycin AptaPharma.

Breastfeeding
Inform your doctor if the patient is breastfeeding, as Vancomycin AptaPharma passes into human milk. The doctor will decide whether vancomycin is truly necessary or whether the patient should stop breastfeeding.

Driving and operating machinery
Vancomycin AptaPharma has no effect or negligible effect on the ability to drive vehicles and operate machinery.

3. How to use Vancomycin AptaPharma

The patient will receive Vancomycin AptaPharma administered by medical personnel during their hospital stay. The doctor will decide the daily dose required 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 has,
• the patient's kidney function,
• the patient's hearing status,
• all other medications the patient is taking.

Intravenous administration
Adults and adolescents (aged 12 years and above)
Dosing will be 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 single dose of 2 g must not be exceeded.

Use in children
Children from 1 month of age and children below 12 years of age
Dosing will be 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 neonates and full-term newborns (from 0 to 27 days)
The dose will be calculated based on post-conceptional 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)].

Different dosing may be required for elderly patients, obese patients, pregnant women, and patients with impaired kidney function, including dialysis patients.

Duration of treatment
The duration of treatment depends on the type of infection present and may range from 1 to 6 weeks.
The duration may vary depending on the individual patient's response to treatment.
During treatment, the patient may undergo blood tests and urine analysis, and hearing tests may be performed to monitor for potential adverse effects.

Oral administration
Adults and adolescents (aged 12 and above)
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 of 2 g must not be exceeded.
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 below 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 of 2 g must not be exceeded.

Method of administration
Intravenous infusion means that the medicine flows from an infusion bottle or bag through a tube into one of the patient's blood vessels. The doctor or nurse will always administer vancomycin into the bloodstream, never into muscle.
Vancomycin must be administered intravenously over at least 60 minutes.

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

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

Overdose of Vancomycin AptaPharma
Since the medicine will be administered during the patient's hospital stay, it is unlikely that vancomycin will be given in excess. In case of any doubts, inform the doctor or nurse immediately.
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, 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 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, oral, throat, nasal, genital or ocular mucosal ulcers. 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, peeling rash with subcutaneous nodules and blisters, accompanied by fever at the beginning of treatment (acute generalized exanthematous pustulosis).
• chest pain, which may be a sign of a potentially serious allergic reaction known as Kounis syndrome.

Vancomycin is poorly absorbed from the gastrointestinal tract. However, if the patient has inflammatory bowel disease, and especially if they also have impaired kidney function, adverse reactions similar to those occurring after intravenous vancomycin infusion may occur.

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 airflow in the upper respiratory tract)
• rash and inflammation of the oral mucosa, itching, itchy rash, urticaria
• impaired kidney function, usually detected in blood tests
• redness of the upper body and face, phlebitis
• 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 types of white blood cells in the blood
• balance disorders, 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 skin allergic 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 in the armpits (lymph node swelling), abnormal blood test results and liver function tests
• blistering rash with fever
• excessive breakdown of red blood cells, leading to fatigue and pale skin (hemolytic anemia)

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

5. How to store Vancomycin AptaPharma

Before reconstitution:
Store below 25 ⁰C.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date (EXP) stated on the label and the cardboard box.
The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.
The stability of the solution after reconstitution and subsequent dilution is provided below in the information for healthcare professionals.

6. Contents of the pack and other information

What Vancomycin AptaPharma contains
The active substance is vancomycin (as hydrochloride).
Vancomycin AptaPharma 500 mg
Each vial contains 500 mg of vancomycin hydrochloride, equivalent to 500,000 IU.
Vancomycin AptaPharma 1000 mg
Each vial contains 1000 mg of vancomycin hydrochloride, equivalent to 1,000,000 IU.

What Vancomycin AptaPharma looks like and contents of the pack
Vancomycin AptaPharma, 500 mg: The powder is contained in a 10 mL vial made of clear, colourless type I glass, with a chlorobutyl rubber stopper and a white aluminium-polypropylene cap, with a self-adhesive identification label.
Vancomycin AptaPharma, 1000 mg: The powder is contained in a 20 mL vial made of clear, colourless type I glass, with a chlorobutyl rubber stopper and a blue aluminium-polypropylene cap, with a self-adhesive identification label.
The carton pack contains 10 vials.

Vancomycin AptaPharma, 500 mg
Each vial contains vancomycin hydrochloride equivalent to 500 mg of vancomycin.
After reconstitution with 10 mL of water for injections, a solution of 50 mg/mL is obtained, which can be further diluted to a concentration of 5 mg/mL.

Vancomycin AptaPharma, 1000 mg
Each vial contains vancomycin hydrochloride equivalent to 1000 mg of vancomycin.
After reconstitution with 20 mL of water for injections, a solution of 50 mg/mL is obtained, which can be further diluted to a concentration of 5 mg/mL.

Marketing Authorisation Holder
Apta Medica Internacional d.o.o.
Likozarjeva Ulica 6
1000 Ljubljana
Slovenia

Manufacturer
Laboratorio Reig Jofré SA
Gran Capità, 10
08970 Sant Joan Despí, Barcelona
Spain

This medicinal product is authorised in the Member States of the European Economic Area under the following names:

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 to the patient, they are necessary for treating a specific, current illness.
Despite antibiotic treatment, some bacteria may survive or continue to multiply. This phenomenon is called resistance; sometimes antibiotic treatment becomes ineffective.
Improper use of antibiotics increases resistance. The patient may even facilitate the development of resistance and thereby delay recovery or reduce the effectiveness of antibiotic therapy if they do not adhere to the proper:

• dosage,
• treatment schedule,
• duration of treatment.

Therefore, to maintain the effectiveness of this medicine, it is essential to:

1. Use antibiotics only when prescribed by a doctor.
2. Strictly follow the prescribed method of use.
3. Do not reuse antibiotics without a doctor's recommendation, even to treat a similar illness.

Information intended exclusively for medical professionals

This information is a fragment of the Summary of Product Characteristics, which is intended to assist in the administration of Vancomycin AptaPharma. When assessing the appropriateness of use in an individual patient, the physician should consult the full Summary of Product Characteristics.

Intravenous administration
For intravenous infusion only. Do not administer intramuscularly.

Preparation of reconstituted solution
Reconstitute the contents of each 500 mg vial with 10 mL of sterile water for injections.
Reconstitute the contents of each 1000 mg vial with 20 mL of sterile water for injections.
One mL of reconstituted solution contains 50 mg of vancomycin.

Appearance of reconstituted solution
After reconstitution, the solution is clear, colourless, and free from particulate matter.

Preparation of ready-to-use diluted solution for infusion
The reconstituted solution containing 50 mg/mL vancomycin must be further diluted.
Appropriate diluents are:

• 50 mg/mL (5%) glucose solution for injection
• 9 mg/mL (0.9%) sodium chloride solution for injection
• Ringer's lactate solution
• Ringer's acetate solution

Intermittent infusion
The reconstituted solution containing 500 mg vancomycin (50 mg/mL) should first be diluted in at least 100 mL of diluent (to achieve 5 mg/mL).
The reconstituted solution containing 1000 mg vancomycin (50 mg/mL) should first be diluted in at least 200 mL of diluent (to achieve 5 mg/mL).
The vancomycin concentration in the infusion solution should not exceed 5 mg/mL.
The required dose should be administered slowly by intravenous infusion at a rate not exceeding 10 mg/min over at least 60 minutes or longer.

Continuous infusion
Should only be used when intermittent infusion is not feasible.
Two to four vials containing 500 mg vancomycin (1–2 g) or one to two vials containing 1000 mg vancomycin (1–2 g) may be dissolved in an appropriate volume of one of the diluents listed above and administered via infusion pump so that the patient receives the prescribed daily dose over 24 hours.

Appearance of diluted solution
After dilution, the solution is transparent, colourless, and free from particulate matter.
Before administration, reconstituted and diluted solutions should be inspected visually for particulate matter and discoloration. Only clear, colourless solutions free from particulates should be used.

Oral administration
For oral administration, solutions containing 500 mg and 1000 mg of vancomycin may be diluted in 30 mL of water and administered to the patient or via a nasogastric tube.

Stability
Stability of reconstituted solution:
The reconstituted solution with water for injections remains chemically stable for 24 hours at 2°C–8°C. From a microbiological standpoint, the solution should be used immediately.

Stability of diluted solution:
Chemical and physical in-use stability has been demonstrated:

• for 8 hours at 25°C after reconstitution and further dilution with 9 mg/mL (0.9%) sodium chloride solution or 50 mg/mL (5%) glucose solution;
• for 4 days at 2°C–8°C after reconstitution and further dilution with Ringer's lactate or Ringer's acetate;
• for 14 days at 2°C–8°C after reconstitution and further dilution with 9 mg/mL (0.9%) sodium chloride solution or 5% glucose solution.

From a microbiological standpoint, the medicinal product should be used immediately.

Patients with renal function impairment
In adult patients and in children and adolescents with impaired renal function, consider administering an initial loading dose followed by monitoring of serum vancomycin trough concentrations, rather than following a fixed dosing schedule, especially in patients with severe renal impairment or those undergoing renal replacement therapy (RRT), due to multiple variables affecting vancomycin concentrations 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 reducing the total daily dose.
Concomitant medicinal products that may reduce vancomycin clearance and/or increase the risk of adverse effects should be appropriately evaluated (see section 4.4 of the SmPC).
Vancomycin is only slightly removed by intermittent haemodialysis. 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 post-dialysis session in the case of intermittent haemodialysis).

Vancomycin solutions have a low pH, which may cause chemical or physical instability when mixed with other substances. Mixing vancomycin with alkaline solutions should be avoided.
This medicinal product must not be mixed with other infusion solutions except 9 mg/mL (0.9%) sodium chloride, 50 mg/mL (5%) glucose, Ringer's lactate, or Ringer's acetate.