Syntarpen

Package leaflet: Information for the patient

Syntarpen, 2 g, powder for solution for injection / infusion
Cloxacillinum
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, inform the doctor, pharmacist, or nurse. See section 4.

Contents of the leaflet

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

1. What Syntarpen is and what it is used for

Syntarpen contains cloxacillin as the active substance, which is an antibiotic belonging to the group of semi-synthetic penicillins. Cloxacillin acts against various strains of Gram-positive and Gram-negative bacteria, but is most commonly used in the treatment of infections caused by methicillin-sensitive staphylococci. Cloxacillin is used in the treatment of infections caused by methicillin-sensitive staphylococci such as:

• Skin and soft tissue infections (e.g. furunculosis);
• Endocarditis, central nervous system infections;
• Lower respiratory tract infections;
• Suppurative complications following burns or surgery;
• Bone and joint infections, mainly post-traumatic – oral formulations are usually used in later stages of treatment;
• Septicaemia (a specific systemic response to infection);
• Osteomyelitis (infection of the bone and bone marrow).

Before starting treatment, the doctor may order a test (antibiogram) to determine the effectiveness of Syntarpen against the bacteria causing the infection. Treatment may be initiated before the test results are available. After receiving the antibiogram results, the doctor may switch to another antibiotic.

2. Important information before using Syntarpen

When not to use Syntarpen
If the patient is allergic to cloxacillin or other beta-lactam antibiotics.

Warnings and precautions
Before starting treatment with Syntarpen, discuss this with your doctor.
➢ If the patient has previously experienced an allergic reaction to any antibiotic or other medicines, or has any other allergic reactions, this should be reported to the doctor before using the medicine.
Hypersensitivity reactions to cloxacillin may occur more frequently in individuals with a tendency toward allergic reactions to various substances and in patients with asthma. These reactions may vary in symptoms and severity – from skin rashes to anaphylactic shock (a severe allergic reaction; see section 4 "Possible side effects"). Therefore, if skin changes (e.g. urticaria, itching) or other symptoms indicating allergy occur during treatment with Syntarpen, the medicine should be discontinued immediately and medical advice should be sought without delay.
➢ If the patient needs to take Syntarpen for a prolonged period, the doctor will usually recommend periodic monitoring of kidney and liver function, as well as peripheral blood morphology.
➢ Prolonged use of antibiotics may lead to overgrowth of resistant bacteria or fungi. If symptoms of new infections occur during treatment with Syntarpen, the medicine should be discontinued and the patient should contact their doctor.
➢ If the patient develops diarrhoea during or after treatment with Syntarpen, this should be reported to the doctor. It may be a sign of pseudomembranous colitis – a complication associated with antibiotic use. In such cases, treatment with the medicine must be stopped and, sometimes, specific treatment may be required. Medicines that inhibit peristalsis or have constipating effects should not be used.
➢ Renal and urinary tract disorders occur most frequently in patients receiving high doses of the medicine and/or those with pre-existing kidney dysfunction, and usually resolve after discontinuation of the medicine. For this reason, during long-term treatment with cloxacillin, the doctor will monitor kidney and liver function, as well as peripheral blood morphology. In cases of renal failure associated with liver dysfunction, the doctor will regularly monitor serum concentrations of cloxacillin.
➢ If the patient has cystic fibrosis, the doctor will monitor cloxacillin blood levels and may consider increasing the dose of the medicine.
In case of doubt, consult a doctor or pharmacist.

Syntarpen and other medicines
Inform the doctor about all medicines currently or recently taken by the patient, as well as any medicines planned for future use.
In particular, inform the doctor if the patient is taking:
probenecid (used in the treatment of gout) – when administered concurrently with Syntarpen, it may increase the antibiotic concentration in blood serum;
anticoagulants (medicines preventing blood clots), such as warfarin – when used together with Syntarpen, they may increase the tendency to bleeding and lead to haemorrhage;
methotrexate (used in the treatment of rheumatoid arthritis) – Syntarpen used together with methotrexate may increase its toxicity;
oral contraceptives – Syntarpen used together with oral contraceptives may reduce contraceptive efficacy. The doctor will recommend using additional non-hormonal contraceptive methods;
ampicillin, fusidic acid (antibiotics) – when used simultaneously with Syntarpen, may show enhanced effects;
erythromycin, tetracyclines, chloramphenicol (antibiotics) – concomitant administration of Syntarpen with any of these medicines may weaken its effect;
aminoglycoside antibiotics (e.g. streptomycin, gentamicin, neomycin) and Syntarpen are physically and chemically incompatible; these medicines should not be administered simultaneously;
proguanil (a medicine used in malaria treatment) may cause decreased serum concentrations of cloxacillin and reduce treatment efficacy.
Patients allergic to cephalosporins may also be allergic to cloxacillin (so-called cross-allergy).

Effect on laboratory test results
In patients receiving Syntarpen, urine glucose tests performed by certain methods may yield false-positive results; therefore, if such testing is necessary, enzymatic tests are recommended.
Syntarpen may also alter the results of urinary steroid assays.

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 before using this medicine.

Pregnancy
For safety reasons, Syntarpen should be used during pregnancy only when, in the doctor's opinion, the potential benefits outweigh the possible risks.

Breastfeeding
The medicine passes into breast milk in small amounts. Therefore, breastfeeding may need to be discontinued if gastrointestinal disturbances (diarrhoea, oral thrush, or skin rash) occur in the infant.
There are only limited data available on the use of cloxacillin in humans. Animal studies on reproductive toxicity are insufficient.

Driving and operating machinery
There are no data available on the effect of Syntarpen on the ability to drive vehicles or operate machinery. Therefore, if the patient experiences symptoms affecting concentration (e.g. headache, drowsiness; see section 4 "Possible side effects"), driving and operating machinery should be avoided.

Syntarpen contains sodium
Each gram of the medicine contains 50.5 mg of sodium (main component of table salt). This corresponds to 2.5% of the maximum recommended daily sodium intake in the adult diet.
This should be taken into account in patients who are monitoring sodium intake in their diet.
When using solvents containing sodium (see "Information intended exclusively for healthcare professionals"), the amount of sodium originating from the solvent should be included in calculating the total sodium content in the prepared dilution. For this purpose, refer to the leaflet of the solvent used.

3. How to use Syntarpen

This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.

Dosage

The dose depends on the severity of the infection, the susceptibility of the causative microorganism, the patient's condition, age, and body weight.

Adults

Depending on the type and severity of infection, 1–2 g should be administered intramuscularly or intravenously every 4–6 hours.

The maximum daily dose is 12 g.

Children and adolescents

Children up to 20 kg body weight – 25 to 50 mg/kg body weight per day, administered intravenously or intramuscularly in 4 divided doses every 6 hours.

Children over 20 kg body weight – 100 to 200 mg/kg body weight per day, administered intravenously or intramuscularly in 4 divided doses every 6 hours. In severe infections such as infective endocarditis caused by Staphylococcus spp., the dose may be increased to 300 mg/kg body weight per day in 4–6 divided doses.

Recommended dosing in specific infections for adults

Pneumonia caused by methicillin-sensitive Staphylococcus aureus

1–2 g intravenously or intramuscularly every 6 hours for 10–14 days.

Pyogenic myositis caused by methicillin-sensitive Staphylococcus aureus

2 g intravenously or intramuscularly every 6 hours for 5–10 days.

Septic arthritis caused by methicillin-sensitive Staphylococcus aureus

2 g intravenously or intramuscularly every 6 hours for 2–3 weeks.

Osteomyelitis caused by methicillin-sensitive Staphylococcus aureus

2 g intravenously or intramuscularly every 6 hours for 4–6 weeks.

Endocarditis caused by methicillin-sensitive Staphylococcus aureus

Native valve – 12 g per day intravenously in 4–6 divided doses for 4–6 weeks.

Prosthetic valve – 12 g per day intravenously in 4–6 divided doses for 6 weeks or longer, together with gentamicin 3 mg/kg body weight per day administered intravenously or intramuscularly in 1–2 doses for 2 weeks, and rifampicin 900–1200 mg per day in 2–3 divided doses, administered intravenously or orally, for 6 weeks or longer.

Note: In severe infections, performing an antibiogram before initiating treatment with cloxacillin is recommended.

Use of the medicine in patients with renal function impairment

Patients with impaired kidney function should inform their doctor before receiving Syntarpen. The doctor will determine the dosage individually depending on the degree of renal impairment (see section 2 "Warnings and precautions").

If during treatment the patient feels that the medicine's effect is too strong or too weak, they should consult their doctor.

Duration of treatment

The duration of treatment depends on the severity and type of infection.

The doctor will determine the appropriate treatment duration, which should be strictly followed.

Instructions for administration and preparation of solutions are provided at the end of this leaflet in the section "Information intended exclusively for healthcare professionals."

Use of a higher than recommended dose of Syntarpen

Since Syntarpen will be administered by a doctor or nurse, incorrect dosing is unlikely. However, if the patient suspects that an excessive dose has been administered, they should immediately inform the doctor.

Missed dose of Syntarpen

Do not administer a double dose to make up for a missed dose.

Discontinuation of Syntarpen treatment

It is important that the medicine is used according to the prescribed treatment regimen. Do not stop treatment simply because the patient feels better. Premature discontinuation of treatment may result in recurrence of infection.

If the patient feels worse during treatment or does not feel well after completing the prescribed treatment course, they should contact their doctor.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody will get them.
Serious adverse reactions
If any of the following serious adverse reactions occur, inform your doctor immediately.
The following serious adverse reactions occur very rarely (less than 1 in 10,000 people):

Allergic reactions, immediate allergic reactions such as sudden shortness of breath and chest tightness, swelling of the eyelids, face or lips, severe skin rashes which may involve blistering affecting the eyes, mouth, throat and genital organs, loss of consciousness (fainting).
Delayed allergic reactions (may occur 48 hours up to 2 and even up to 4 weeks after starting treatment) such as fever, malaise, urticaria, muscle pain, joint pain, abdominal pain, skin rashes, erythema multiforme, rapidly developing severe rash with blisters or peeling skin and possible blisters in the mouth (Stevens-Johnson syndrome), formation of blisters which, when ruptured, lead to oozing erosions and the epidermis detaches in sheets (toxic epidermal necrolysis; Lyell's syndrome), serum sickness-like symptoms such as skin urticaria with burning sensation, allergic vasculitis.
Diarrhea that is severe, persistent or contains blood, accompanied by abdominal pain or fever. This may be a sign of a serious intestinal inflammation (called pseudomembranous colitis), which may occur after antibiotic use.

Other adverse reactions that may occur during treatment
The following adverse reactions occur frequently (not more than 1 in 10 people):

• Diarrhea.

The following adverse reactions occur rarely (less than 1 in 1,000 people):

• Skin redness at the injection site or thrombophlebitis.

The following adverse reactions occur very rarely (less than 1 in 10,000 people):

• Increased or decreased count of certain types of white or red blood cells and platelets, abnormal breakdown of red blood cells, bone marrow suppression;
• Nausea, vomiting, stomatitis, black discoloration of the tongue;
• Anuria, interstitial nephritis, tubular kidney dysfunction. Symptoms of these disorders usually include rash, fever, increased count of one type of granulocytes in blood, haematuria, proteinuria. These usually occur in patients receiving high doses of the drug and (or) with pre-existing kidney dysfunction and resolve after discontinuation of the drug;
• Transient hyperkinesia, restlessness, agitation, drowsiness, disorientation and (or) dizziness. These symptoms usually occur in patients with renal insufficiency receiving high doses of the drug;
• Increased liver enzyme activity; in isolated cases, hepatitis may occur, jaundice of the skin and whites of the eyes (signs of cholestatic jaundice due to bile stasis). These symptoms resolve after discontinuation of the drug;
• Fever, headache and dizziness – resolve after discontinuation of the drug.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, tell 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.
By reporting adverse reactions, additional information on the safety of the medicine can be collected.

5. How to store Syntarpen

Store below 30ºC.
Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date (EXP) stated on the packaging. 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. This will help protect the environment.

6. Contents of the package and other information

What Syntarpen contains
The active substance is cloxacillin in the form of cloxacillin sodium.
One vial contains 2 g of cloxacillin in the form of cloxacillin sodium.
The medicine does not contain any other ingredients.

What Syntarpen looks like and contents of the pack
White or almost white crystalline powder.
The pH value of the prepared solution is 5.0 ÷ 7.0.
Packaging: One vial in a cardboard box.

Marketing Authorisation Holder and Manufacturer
Tarchomin Pharmaceutical Works "Polfa" Joint Stock Company
A. Fleminga 2 Street
03-176 Warsaw
Telephone number: (22) 811-18-14

For further information about this medicine, please contact the Marketing Authorisation Holder.

Information intended exclusively for medical professionals

Preparation of solutions
Administration method
Intramuscular injection
The medicinal product should be injected into large muscle groups. Doses exceeding 1 g should be administered into two separate sites.
Intravenous injection
For intravenous bolus injections, cloxacillin should be administered over 2 to 10 minutes.
For intravenous infusion, cloxacillin should be administered over 30–40 minutes.
Preparation method
Intramuscular injection
Dissolve 2 g of powder in 8 ml of water for injections or 0.9% sodium chloride solution.
Intravenous injection
Dissolve 2 g of powder in 20 ml of water for injections or 0.9% sodium chloride solution. Administer slowly over 2 to 10 minutes.
The prepared solutions may be stored for 12 hours at a temperature below 25°C.
Intravenous infusion
Dissolve the contents of a 2 g vial in 8 ml of water for injections, then dilute with 0.9% sodium chloride solution or 5% glucose solution to a final volume of 50 ml.
Administer over 30 to 40 minutes. Concentrations exceeding 40 mg/ml are not recommended.
The prepared solution may be stored for 12 hours at a temperature below 25°C or for 48 hours at 2°C–8°C (in a refrigerator).
Stability of prepared cloxacillin solutions stored in containers made of PVC

Stability of prepared cloxacillin solutions stored in containers made of polyolefin

The physicochemical stability of cloxacillin solutions for injection is maintained for
12 hours at temperatures below 25°C, whereas infusion solutions can be stored for 12 hours at
temperatures below 25°C or for 48 hours at 2°C–8°C (in a refrigerator).
From a microbiological standpoint, the medicinal product should be used immediately. If not used
immediately, the user is responsible for the conditions and duration of storage.
Pharmaceutical incompatibilities
Cloxacillin should not be mixed with aminoglycosides, tetracyclines, erythromycin, polymyxin B,
or blood products and protein hydrolysates. If co-administration of cloxacillin with another medicinal product is necessary, both products should be administered separately at different sites, with approximately one hour interval between administrations.