VANCOMYCIN MIP 500 mg POWDER FOR SOLUTION FOR INFUSION

2. What you need to know before you use Vancomycin MIP

Do not use Vancomycin MIP

• if you are allergic to vancomycin or any of the other components of this medication (listed in section 6).

Warnings and precautions

Severe side effects have been reported that can cause loss of vision after injection of vancomycin into the eyes.

Talk to your doctor or hospital pharmacist or nurse before using this medication if:

• You have had an allergic reaction to teicoplanin, as this may also mean you are allergic to vancomycin.
• You have a hearing problem, especially if you are an elderly person (you may need hearing tests during treatment).
• You have kidney problems (you will need to have blood tests and kidney function tests during treatment).
• You are being given vancomycin by infusion for the treatment of diarrhea associated with Clostridium difficileinfection instead of orally.
• You have ever developed a severe rash or skin peeling, blisters, and/or sores in the mouth after taking vancomycin.

Talk to your doctor or hospital pharmacist or nurse during treatment with Vancomycin MIP if:

• You are being given vancomycin for a long time (you may need to have blood tests, liver function tests, or kidney function tests during treatment).
• You develop any skin reaction during treatment.
• Consult your doctor immediately if you develop severe or chronic diarrhea during or after using vancomycin. This can be a sign of intestinal inflammation (pseudomembranous colitis) that can occur after antibiotic treatment.

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 in association with vancomycin treatment. Stop using vancomycin and seek medical attention immediately if you notice any of the symptoms described in section 4.

Children

Vancomycin is used with special care in premature and small babies, as their kidneys are not fully developed and may accumulate vancomycin in the blood. To control vancomycin blood levels in this age group, blood tests are performed.

The simultaneous administration of vancomycin and anesthetic agents has been associated with skin redness (erythema) and allergic reactions in children. Similarly, the simultaneous use with other medications such as aminoglycoside antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen), or amphotericin B (a medication to treat fungal infections) may increase the risk of kidney damage, and therefore, more frequent kidney and blood tests will be necessary.

Using Vancomycin MIP with other medications

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medications.

• Medications that can harm the kidneys and ears:If you take vancomycin at the same time as other medications that can harm the kidneys and ears (e.g., some aminoglycoside antibiotics, piperacillin/tazobactam), this harmful effect may be increased. In that case, thorough and periodic monitoring of kidney and hearing function is necessary.
• Anesthetics:The use of anesthetics increases the risk of certain side effects associated with vancomycin, such as low blood pressure, skin redness, hives, and itching.
• Muscle relaxants:If you use muscle relaxants (such as succinylcholine) at the same time, the effects may be intensified or prolonged.

Pregnancy, breastfeeding, and fertility

Consult your doctor or pharmacist before taking any medication.

Vancomycin crosses the placenta, and there is a risk of toxicity to the fetus's ears and kidneys. Therefore, if you are pregnant, your doctor should administer vancomycin only if it is clearly necessary and after a careful study of the benefits and risks.

Vancomycin passes into breast milk. Since the baby may be affected by this medication, it should only be used during breastfeeding if other antibiotics have not been effective. Consult your doctor about the possibility of stopping breastfeeding.

Driving and using machines

Vancomycin MIP does not affect or has negligible effects on the ability to drive and use machines.

3. How to use Vancomycin MIP

Medical staff will administer vancomycin to you during your hospital stay. Your doctor will decide the amount of medication you should receive each day and how long the treatment will last.

Dosage

The dose administered will depend on:

• your age,
• your weight,
• the infection you have,
• kidney function,
• your hearing ability,
• any other medication you are taking.

Intravenous administration

Adults and adolescents (from 12 years and older)

The dose will be calculated according to your body weight. The usual infusion dose is 15 to 20 mg per kg of body weight. It is usually administered every 8 to 12 hours. In some cases, the doctor may decide to give an initial dose of up to 30 mg per kg of body weight. The maximum daily dose should not exceed 2 g.

Use in children

Children aged 1 month to less than 12 years

The dose will be calculated according to your body weight. The usual infusion dose is 10 to 15 mg per kg of body weight. It is usually administered every 6 hours.

Preterm and term newborns (from 0 to 27 days)

The dose will be calculated according to the postmenstrual age (time between the first day of the last menstrual period and birth (gestational age) plus the time after birth (postnatal age).

Elderly patients, pregnant women, and patients with kidney disorders, including those on dialysis, may need a different dose.

Method of administration

Intravenous infusion means that the medication flows from an infusion bottle or bag through a tube into one of your blood vessels and into your body. Your doctor or nurse will always administer vancomycin into the blood and not into the muscle.

Vancomycin is administered into the vein over at least 60 minutes.

Duration of treatment

The duration of treatment depends on the infection and can last several weeks.

The duration of therapy may be different depending on the individual response to treatment for each patient.

During treatment, blood samples, urine samples, and possibly hearing tests will be taken to look for signs of possible side effects.

If you use more Vancomycin MIP than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to use Vancomycin MIP

Do not take a double dose to make up for forgotten doses. A forgotten dose can only be administered before the next scheduled dose if the interval between them is wide enough.

In case of interruption or premature suspension of treatment with Vancomycin MIP

Low doses, irregular administration, or premature suspension of treatment may compromise the outcome of the treatment or cause relapses with more complicated treatment. Always follow your doctor's instructions.

If you have any further questions on the use of this medication, ask your doctor or pharmacist.

4. Possible side effects

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

Stop using vancomycin and seek medical attention immediately if you notice any of the following symptoms:

• Reddish patches, like targets or circular, on the trunk, often with central blisters, skin peeling, mouth ulcers, throat, nose, genitals, and eyes. These severe skin rashes can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome and toxic epidermal necrolysis).
• Widespread rash, high body temperature, and swollen lymph nodes (DRESS or drug hypersensitivity syndrome).
• Red, scaly, and widespread rash with bumps under the skin and blisters accompanied by fever at the start of treatment (acute generalized exanthematous pustulosis).

Vancomycin can cause allergic reactions, although severe allergic reactions (anaphylactic shock) are rare. Tell your doctor immediately if you notice any sudden wheezing, difficulty breathing, redness in the upper body, skin rash, or itching.

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

• Low blood pressure
• Shortness of breath, wheezing
• Oral mucosa inflammation, itching, itchy rash, hives
• Kidney problems that can be detected by a blood test
• 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 white blood cells, red blood cells, and platelets (cells responsible for blood clotting)

Increase in some of the white blood cells in the blood.

• Loss of balance, ringing in the ears, dizziness
• Blood vessel inflammation
• Nausea (feeling of discomfort)
• 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 appearance of a severe allergic reaction on the skin, with peeling or blistering. This can be associated with high fever and joint pain
• Cardiac arrest
• Intestinal inflammation, which causes abdominal pain and diarrhea (which may contain blood)

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

• Vomiting, diarrhea
• Confusion, drowsiness, lack of energy, swelling, fluid retention, decreased urine output
• Rash with swelling or pain behind the ears, in the neck, groin, under the chin, and armpits (inflamed lymph nodes), abnormal blood tests, and liver function tests.
• Rash with blisters and fever.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report side effects directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Vancomycin MIP

Keep this medication out of sight and reach of children.

Store below 25°C. Keep in the original packaging to protect from light.

Do not use this medication after the expiry date stated on the outer packaging and on the label after "EXP". The expiry date is the last day of the month indicated.

Do not use this medication if you notice particles or discoloration of the infusion solution.

Medicines should not be disposed of via wastewater or household waste. Place the packaging and any unused medication in the SIGRE 1 collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Container Content and Additional Information

Composition of Vancomycin MIP

• The active ingredient is vancomycin. Each vial contains 500 mg of vancomycin hydrochloride, equivalent to 500,000 UI of vancomycin.
• It does not contain other excipients.

Appearance of the Product and Container Content

Fine white powder with slight shades of pink and brown tones.

Vancomycin MIP is available in packages of 1 or 5 glass vials with a rubber stopper and a "flip-off" seal.

Marketing Authorization Holder

MIP Pharma GmbH

Kirkeler Str. 41

66440 Blieskastel

Germany

Phone 0049-6842/9609-0

Fax 0049-6842/9609-355

Manufacturer

Chephasaar Chem.-Pharm. Fabrik GmbH

Mühlstr. 50

66386 St. Ingbert

Germany

Date of the Last Revision of this Prospectus: 03/2021.

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

Other Sources of Information

Medical Advice/Education

Antibiotics are used to cure infections caused by bacteria. They are ineffective against infections caused by viruses.

If your doctor has prescribed antibiotics, you need them precisely to treat your current illness.

Despite antibiotics, some bacteria may survive or grow. This phenomenon is known as resistance: some antibiotic treatments become ineffective.

Misuse of antibiotics increases resistance. You can even help bacteria become resistant and thus delay your recovery or decrease the effectiveness of antibiotics if you do not respect the following:

• the dose
• the schedule
• the duration of treatment

Therefore, to preserve the effectiveness of this medication:

1 - Use antibiotics only when prescribed.

2 - Strictly follow the prescription instructions

3 - Do not reuse an antibiotic without a medical prescription, even if you want to treat a similar illness.

-------------------------------------------------------------------------------------------------------------------

This information is intended only for healthcare professionals:

The powder must be reconstituted and the resulting concentrate must be diluted subsequently before use.

Preparation of the Concentrate for Infusion

Dissolve the contents of each 500 mg vial in 10 ml of sterile water for injectable preparations.

One ml of the reconstituted solution contains 50 mg of vancomycin hydrochloride.

Preparation of the Infusion Solution

The infusion concentrate can be diluted in sterile water for injectable preparations, sodium chloride at 9 mg/ml, or glucose at 50 mg/ml.

500 mg vial: to obtain a 5 mg/ml infusion solution, dilute 10 ml of the infusion concentrate with 90 ml of diluent.

The concentration of vancomycin hydrochloride in the infusion solution cannot exceed 2.5-5 mg/ml.

Appearance of the Infusion Solution

The solution must be visually examined for particles or discoloration before administration.

The solution can only be used if it is clear and does not contain particles.

Compatibility with Intravenous Solutions

Vancomycin is compatible with water for injectable preparations, 5% glucose solutions, and physiological sodium chloride solutions. Vancomycin solutions are administered basically separately if their chemical and physical compatibility with another infusion solution has not been demonstrated.

To avoid precipitation due to the low pH of vancomycin hydrochloride in solution, all intravenous cannulas and catheters must be flushed with physiological serum.

Important Incompatibilities

Vancomycin solutions have a low pH, which can produce chemical or physical instability after mixing with other substances. Therefore, parenteral solutions must be visually checked for precipitations or color changes before use.

Vancomycin solutions are not compatible with penicillin or cephalosporin solutions (beta-lactam antibiotics). The risk of precipitation increases when the vancomycin concentration is higher. To avoid precipitation, intravenous cannulas and catheters must be flushed with saline solution between the administration of vancomycin and these antibiotics.

Combined Treatments

In the case of combined treatments of vancomycin with other antibiotics or chemotherapeutic products, preparations must be administered separately.

Storage after Reconstitution

Validity Period of the Infusion Solution

The chemical and physical stability of the prepared infusion solution has been verified for 96 hours between 2-8°C. From a microbiological point of view, the product must be used immediately. If not, the user will be responsible for the storage times and conditions before use, and the storage time must not exceed 24 hours between 2-8°C, unless the reconstitution/dilution has taken place in validated and controlled aseptic conditions.

Mode of Application and Duration of Treatment

Vancomycin is only administered as a slow intravenous infusion, lasting at least one hour or at a maximum rate of 10 mg/min (whichever is longer), and must be sufficiently diluted (at least 100 ml per 500 mg or at least 200 ml per 1,000 mg).

Patients with fluid restrictions can receive a 500 mg/50 ml or 1,000 mg/100 ml solution, taking into account that the risk of unwanted effects related to infusion may increase at high concentrations.

A hypersensitive reaction (anaphylactic/anaphylactoid) may occur during or immediately after a rapid infusion of vancomycin.

Rapid administration (i.e., over several minutes) may cause excessive hypotension (including reactions and, less frequently, cardiac arrests), histamine-like reactions, and erythematous or maculopapular eruptions ("red man syndrome"). In the event of severe hypersensitive reactions (e.g., anaphylactic reaction), treatment with vancomycin should be immediately discontinued and standard emergency measures should be taken.

The simultaneous use of vancomycin and anesthetics increases the risk of trunk reddening and allergic reactions. To reduce the risk of these reactions, vancomycin should be administered over a period of 60 minutes before anesthetics.