Vancomycin swiss2care

Package leaflet: Information for the patient

VANCOMYCIN Swiss2Care
1 g, powder for solution for infusion and oral solution
Vancomycinum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or hospital pharmacist or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, hospital pharmacist or nurse. See section 4.

Contents of the leaflet

1. What Vancomycin Swiss2Care is and what it is used for
2. Important information before using Vancomycin Swiss2Care
3. How to use Vancomycin Swiss2Care
4. Possible side effects
5. How to store Vancomycin Swiss2Care
6. Contents of the pack and other information

1. What Vancomycin Swiss2Care is and what it is used for

Vancomycin is an antibiotic belonging to the glycopeptide class of antibiotics. Vancomycin works by killing certain bacteria that cause infections.
Vancomycin in powder form is used to prepare a solution for infusion or an oral solution.
Indications
Intravenous use
Vancomycin is administered by infusion (intravenous drip) in all age groups for the treatment of the following serious infections:

• skin and soft tissue infections;
• bone and joint infections;
• lung infections known as pneumonia;
• infection of the inner lining of the heart (endocarditis);
• bloodstream infections associated with the above-mentioned infections.

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

2. Important information before using Vancomycin Swiss2Care

When not to use Vancomycin Swiss2Care

• if the patient is allergic to vancomycin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Severe adverse reactions have occurred when vancomycin has been administered into the eye, which may lead to loss of vision.
Before starting treatment with Vancomycin Swiss2Care, discuss with your 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 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 will be required during treatment),
• the patient is receiving vancomycin by infusion for the treatment of diarrhoea associated with Clostridium difficile infection, 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 treatment. If the patient notices any of the symptoms described in section 4, vancomycin treatment must be discontinued immediately and medical advice must be sought without delay.
During treatment with Vancomycin Swiss2Care, discuss with your 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 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 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 necessary to monitor vancomycin blood levels.
Concomitant administration of vancomycin and anaesthetic agents in children has been associated with skin flushing (erythema) and allergic reactions. Additionally, concomitant use with other medicines 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 and kidney function tests may be required.
Vancomycin Swiss2Care and other medicines
Inform your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient intends to take.
Exercise particular caution if the patient is taking other medicines that may interact with vancomycin, such as:

• nephrotoxic (kidney-damaging) and ototoxic (hearing-damaging) drugs (e.g. piperacillin with tazobactam) – these may mutually enhance their adverse effects; particular caution is required when aminoglycosides are used concomitantly with or immediately after vancomycin,
• anaesthetic agents – may increase the risk of hypotension, skin redness, flushing, urticaria and itching (see section 4. Possible side effects),
• muscle relaxants – vancomycin may potentiate and prolong the effects of drugs used during surgery to reduce muscle tone, such as succinylcholine (neuromuscular blockade).

Use of Vancomycin Swiss2Care in elderly patients
The natural age-related decline in glomerular filtration rate may lead to increased vancomycin plasma concentrations if the dose is not appropriately adjusted (see "Dosage in patients with renal impairment").

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
There are insufficient data on the use of vancomycin during pregnancy and breastfeeding in humans. Vancomycin may be administered to pregnant women only if the benefit to the mother outweighs the potential risk to the foetus.
Animal studies have not shown any teratogenic effects of the drug.
Vancomycin passes into human milk; therefore, breastfeeding should be discontinued during treatment to avoid adverse effects in the breastfed infant.

Driving and operating machinery
No data available.

3. How to use Vancomycin Swiss2Care

The patient will receive Vancomycin Swiss2Care administered by medical personnel during hospitalization. The doctor will decide the daily dose to be administered 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 status,
• the patient's hearing status,
• any other medications the patient is taking.

Intravenous administration
Adults and adolescents (aged 12 years and older)
Dosing 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 30 mg per kg of body weight. The maximum daily dose should not exceed 2 g.

Use in children
Children from one month of age and children under 12 years of age
Dosing will be determined based on the patient's body weight. The usual infusion dose is 10 to 15 mg per kg of body weight. This dose is usually administered every 6 hours.

Preterm neonates and full-term newborns (from 0 to 27 days)
The dose will be calculated based on postconceptional age [the time elapsed from the first day of the mother's last menstrual period to delivery (gestational age) plus the time elapsed after birth (postnatal age)].

In elderly patients, pregnant women, and patients with impaired kidney function, a different dose may be required.

Oral administration
Adults and adolescents (aged 12 to 18 years)
The recommended dose is 125 mg every 6 hours. In certain 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 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 a bottle or infusion bag through a tube into one of the patient's veins. The doctor or nurse will always administer vancomycin into the bloodstream, never into muscle.

Vancomycin will be administered intravenously over at least 60 minutes.

Oral administration method
When used to treat gastrointestinal disorders (so-called pseudomembranous colitis), the medicine must be administered as an oral solution (the patient will take the medicine orally).

The contents of one vial of Vancomycin Swiss2Care should be dissolved in 20 ml of water. Individual doses (e.g. 2.5 ml = 125 mg of vancomycin) can be drawn up and administered to the patient diluted in a small volume, either for oral intake or via a gastric tube. A taste-improving agent, such as commonly used syrups, may be added to the prepared solution before administration.

Intravenous administration method
Detailed instructions are provided at the end of this leaflet under the section “Information intended exclusively for healthcare professionals.”

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 also be conducted to monitor for possible adverse effects.

Administration of a higher than recommended dose of Vancomycin Swiss2Care
Treatment in case of overdose:

• no specific antidote is known;
• high plasma concentrations of vancomycin can be effectively reduced by hemodialysis using polysulfone membranes, as well as by hemofiltration or hemoperfusion using polysulfone resins;
• in case of overdose, symptomatic treatment is required, along with maintenance of kidney function. If an excessive dose has been taken, seek immediate medical advice from a doctor or pharmacist.

Missed dose of Vancomycin Swiss2Care
Do not administer a double dose to make up for a missed dose.
If you have any further doubts concerning the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If the patient notices any of the following symptoms, vancomycin treatment should be discontinued immediately and the patient should contact a doctor without delay:

• red, flat, target-like or circular patches on the trunk, often with blisters in the center, skin peeling, 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, peeling rash with subcutaneous nodules and blisters accompanied by fever at the beginning of treatment (acute generalized exanthematous pustulosis).

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 treating physician must be notified immediately.
Vancomycin is negligibly absorbed from the gastrointestinal tract. However, if the patient has an inflammatory condition of the gastrointestinal tract, and especially if kidney function is also impaired, adverse reactions may occur similar to those seen after intravenous infusion of vancomycin.

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

• drop 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 oral mucosa, itching, itchy rash, urticaria,
• kidney function disturbances, usually detectable in blood tests,
• redness of the upper body and face, phlebitis.

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,
• 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 blister formation. 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,
• blistering rash with fever.

Reporting of adverse reactions
If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, inform your doctor, hospital pharmacist, or nurse. Adverse reactions can be reported directly to the Department for Monitoring of Adverse Drug Reactions at the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +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 or parallel importer.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Vancomycin Swiss2Care

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Expiry date". The expiry date refers to the last day of the stated month.
Do not store above 25°C.

Solution stability
The product should be used immediately after reconstitution/dilution. If not used immediately, the conditions and duration of storage prior to use are the responsibility of the user; usually storage should not exceed 24 hours, and the product should be stored at 2°C to 8°C, unless reconstitution/dilution was carried out under controlled and validated aseptic conditions.
The prepared solution remains stable for 4 days when stored at 2°C to 8°C and for 2 days when stored at 20°C to 25°C.

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 package and other information

What Vancomycin Swiss2Care contains

• The active substance is vancomycin. One vial contains 1 g of vancomycin (as 1020 mg hydrochloride), equivalent to 1,000,000 IU of vancomycin.

The medicine does not contain any other ingredients.
What Vancomycin Swiss2Care looks like and contents of the pack
Vial made of colourless glass of type I, in a cardboard box.
For more detailed information, please contact the responsible entity or the parallel importer.
Marketing Authorisation Holder in Italy, country of export, and manufacturer:
Pharmatex Italia Srl, Via S. Paolo, 1, 20121 Milan, Italy
Parallel importer:
Swiss2Care Sp. z o.o. Sp. k.
ul. Mostowa 38/1
87-100 Toruń
Repackaged in:
CEFEA Sp. z o.o. Sp. k.
ul. Działkowa 56
02-234 Warsaw
Marketing Authorisation number in Italy, country of export: 034632024
Parallel import licence number: 214/23
Medical advice and education
Antibiotics are used to treat bacterial infections. They are ineffective against viral infections.
If your doctor has prescribed antibiotics, they are necessary for treating a specific, current illness.
Despite antibiotic use, some bacteria may survive or continue to multiply. This phenomenon is known as resistance; it causes antibiotic treatment to sometimes fail.
Improper use of antibiotics promotes the development of resistance. Patients can also contribute to the emergence of resistance, thereby delaying recovery or reducing the effectiveness of antibiotic therapy, if they do not adhere to the correct:

• dosage,
• treatment schedule,
• duration of treatment. Therefore, to maintain the effectiveness of this medicine, you must: 1 – use antibiotics only when prescribed by a doctor. 2 – strictly follow the prescribed instructions for use. 3 – not reuse antibiotics without a doctor's recommendation, even to treat a similar illness.

Information intended exclusively for medical professionals:

Antibacterial spectrum of activity
Vancomycin is active against Gram-positive bacteria such as staphylococci, streptococci,
enterococci, pneumococci, and Clostridium. Gram-negative bacteria are resistant.
In some cases, an increasing number of resistance cases has been observed, particularly
among enterococci; especially concerning is the occurrence of multidrug-resistant strains
of Enterococcus faecium.
Cross-resistance occurs with other glycopeptide antibiotics, such as teicoplanin.
Bacterial culture samples should be obtained to isolate and identify causative microorganisms
and to determine their susceptibility to vancomycin.

Dosing
In appropriate cases, vancomycin should be administered in combination with other
antibacterial agents.

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.

Patients aged 12 years and older
Recommended dose is 15 to 20 mg/kg body weight every 8 to 12 hours (doses exceeding 2 g per dose should not be used).
In critically ill patients, a loading dose of 25–30 mg/kg body weight may be administered to facilitate rapid achievement of the target minimum serum vancomycin concentration.

Neonates from one month of age and children under 12 years of age:
Recommended dose is 10 to 15 mg/kg body weight every 6 hours.

Term neonates (from birth up to 27 days postnatal age) and preterm neonates (from birth up to expected date of delivery plus 27 days)
To determine the appropriate dosing regimen for neonates, advice should be sought from a physician experienced in treating neonates. One possible vancomycin dosing regimen for neonates is presented in the table below:

PMA: postconceptional 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 48–72 hours.
** In the case of prosthetic joint infections, consider longer cycles of oral
suppressive antibiotic therapy appropriate for prosthetic joint infections.
*** The duration and need for combination therapy depend on the type of valve and
microorganism involved.

Special patient groups

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, consider administering an initial loading dose, followed by monitoring of vancomycin trough serum concentrations rather than adhering to a fixed dosing schedule, especially in patients with severe renal impairment or undergoing renal replacement therapy (RRT), 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 dosing intervals 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 filtration membranes or continuous renal replacement therapy (CRRT) increases vancomycin clearance, and supplemental doses are generally required (usually administered after a 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: [Body weight (kg) × (140 − age in years)] / [72 × serum creatinine concentration (mg/dL)]
Women: 0.85 × value calculated using the above formula.
The usual initial dose for adult patients is 15 to 20 mg/kg; this dose may be administered every 24 hours to patients with a creatinine clearance between 20 and 49 mL/min. In patients with severe renal impairment (creatinine clearance <20 mL/min) or those undergoing renal replacement therapy, appropriate dosing intervals and dose amounts largely depend on the RRT method used and should be determined based on vancomycin trough serum concentrations and residual renal function.
Depending on the clinical situation, administration of the next dose may be withheld until vancomycin serum concentration measurements are available.
In critically ill patients with renal impairment, the initial loading dose should not be reduced.

Children and adolescents
Dose adjustments in pediatric and adolescent patients aged 1 year and older may be based on estimated glomerular filtration rate (eGFR) using the modified Schwartz formula:
eGFR (mL/min/1.73m²) = (height in cm × 0.413) / serum creatinine concentration (mg/dL)
eGFR (mL/min/1.73m²) = (height in cm × 36.2) / serum creatinine concentration (μmol/L)
For neonates and infants under 1 year of age, expert consultation is recommended, as the Schwartz formula is not applicable in these patients.
General 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 serum vancomycin concentrations prior to administration and residual kidney 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 mild hepatic impairment.
Pregnancy
In pregnant women, significantly higher doses may be required to achieve therapeutic serum concentrations.
Obese patients
In obese patients, the initial dose should be individually adjusted according to total body weight, just as in patients with normal body weight.
Oral administration
Patients aged 12 years and older
Treatment of infections caused by Clostridium difficile (Clostridium difficile infection, CDI).
The recommended dose of vancomycin is 125 mg every 6 hours for 10 days in the case of a first, non-severe episode of CDI. 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 using 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 dose of vancomycin is 10 mg/kg body weight every 6 hours for 10 days. The maximum daily dose should not exceed 2 g.
Adjustment of vancomycin treatment duration may be necessary depending on the individual clinical course of the disease. Whenever possible, the antibacterial agent suspected of causing CDI should be discontinued. Adequate fluid and electrolyte replacement should be ensured.
Monitoring serum vancomycin concentrations
The frequency of therapeutic drug monitoring (TDM) 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 once weekly in stable patients showing a clear response to therapy. In patients with normal renal function, serum vancomycin concentration should be measured on the second day of treatment, immediately before the next dose.
In patients undergoing intermittent hemodialysis, vancomycin concentration should be measured before the start of 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 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, i.e., 200 mL per 1000 mg).
Patients with restricted fluid intake may receive a solution of 500 mg/50 mL (1000 mg/100 mL); however, with such higher concentrations, the risk of infusion-related adverse effects increases.
Preparation of the solution
Before use, the dry substance should be dissolved in water for injections. The resulting solution should then be further diluted with compatible injection solutions (see section “Pharmaceutical incompatibilities” below).
The contents of a vial should be dissolved in 20 mL of water for injections, then further diluted with infusion solutions to a final volume of at least 200 mL.
The powder should be dissolved in such volume of solvent that the concentration of the infusion solution does not exceed 5 mg/mL (i.e., 1 g/200 mL).
Continuous infusion of vancomycin may be considered, e.g., in patients with unstable vancomycin clearance.
Oral administration
The contents of one vial should be dissolved in 20 mL of water.
Single doses (e.g., 2.5 mL = 125 mg vancomycin) can be withdrawn from the prepared solution and administered orally to the patient in a small volume or administered via a gastric tube. Flavoring agents, such as commonly used syrups, may be added to the solution.
Pharmaceutical incompatibilities
Vancomycin solutions have a low pH value. Mixing them with other substances may lead to chemical or physical instability. Each parenteral solution should be visually inspected for precipitates or discoloration before administration. Cloudiness of the solution occurs if vancomycin solution is mixed with the following substances:
aminophylline, barbiturates, benzylpenicillin, chloramphenicol sodium succinate, sodium chloride of chlorothiazide, dexamethasone disodium phosphate, sodium heparin, hydrocortisone sodium succinate, methicillin sodium, sodium bicarbonate, nitrofurantoin sodium, novobiocin sodium, phenytoin sodium, sulfadiazine sodium, diethanolamine sulfafurazole.
Compatibility with intravenous fluids
The following fluids may be used to prepare the infusion solution:

• water for injections – for reconstitution of powder only;
• 5% glucose solution;
• 0.9% NaCl solution;
• 5% glucose solution with 0.9% NaCl solution.
  Vancomycin solution should generally be administered separately unless its physicochemical compatibility with a given injection solution has been demonstrated.

Concomitant therapy
If concomitant therapy with vancomycin and other antibiotics or chemotherapeutic agents is used, these products should be administered separately.