Cloxacillin polpharma

Package leaflet: Information for the patient

Cloxacillin Polpharma, 500 mg, powder for solution for injection / infusion
Cloxacillin Polpharma, 1 g, powder for solution for injection / infusion
Cloxacillin Polpharma, 2 g, powder for solution for injection / infusion
Cloxacillinum
Please read the entire leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, 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 others, even if their symptoms are the same.
• If you experience any adverse reactions, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

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

1. What Cloxacillin Polpharma is and what it is used for

Cloxacillin Polpharma contains cloxacillin as the active substance, which is an antibiotic belonging to the group of semi-synthetic penicillins. Cloxacillin is used in infections caused by methicillin-sensitive staphylococci and/or streptococci.
Cloxacillin is used in the treatment of infections caused by methicillin-sensitive staphylococci and/or streptococci, such as:

• Skin and soft tissue infections;
• Endocarditis;
• Central nervous system infections;
• Lower respiratory tract infections;
• Vascular line-related infections;
• Purulent complications following burns and surgery;
• Osteoarticular infections, mainly post-traumatic – in the later stages of treatment, oral formulations are administered;
• Sepsis, septic shock, and toxic shock syndrome (note: in life-threatening conditions requiring immediate treatment initiation, administration of a narrow-spectrum antibiotic without certainty of the infectious agent may be ineffective and result in death);
• Osteomyelitis.

Before starting treatment, your doctor may order a test (antibiogram) to determine the effectiveness of Cloxacillin Polpharma against the bacteria causing the infection. Treatment may be initiated before receiving the test results. After obtaining the antibiogram results, your doctor may change the antibiotic.
When prescribing cloxacillin, the doctor will take into account official guidelines regarding the appropriate use of antibacterial agents.

2. Important information before using Cloxacillin Polpharma

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

Warnings and precautions
Before starting treatment with Cloxacillin Polpharma, discuss this with your doctor.
If the patient has previously experienced an allergic reaction to any antibiotic or other
medicines, or any other allergic reaction, this should be reported to the doctor before using
the medicine. Hypersensitivity reactions to cloxacillin may occur more frequently in individuals
with a tendency towards allergic reactions to various substances and in patients with asthma.
These reactions may present with various symptoms and severity – from skin rashes to anaphylactic shock
(severe allergic reaction; see section 4 "Possible adverse effects"). Therefore, if skin changes (e.g.
urticaria, itching) or other symptoms indicating allergy occur during treatment with Cloxacillin Polpharma,
the medicine should be discontinued immediately and the patient should contact their doctor without delay.
If the patient needs to take Cloxacillin Polpharma for a prolonged period, the doctor will usually order
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 appear during treatment with Cloxacillin Polpharma, the medicine should be discontinued and
the patient should contact their doctor.
If the patient develops diarrhoea during or after treatment with Cloxacillin Polpharma, this should be reported
to the doctor. This may be a symptom of pseudomembranous colitis – a complication associated with
antibiotic use. In such cases, treatment must be discontinued and, sometimes, appropriate therapy initiated.
Medicines that inhibit peristalsis or have constipating effects must not be used.
Renal and urinary tract disorders occur most frequently in patients receiving high doses of the medicine and/or
who already have pre-existing kidney dysfunction, and usually resolve after discontinuation of the medicine
(see section 4 "Possible adverse effects"). For this reason, during prolonged 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 function abnormalities, the doctor will regularly monitor serum concentrations of cloxacillin.
If the patient suffers from cystic fibrosis, the doctor will monitor cloxacillin blood levels and may consider increasing
the dose.
In case of any doubts, consult your doctor or pharmacist.

Cloxacillin Polpharma and other medicines
Inform your doctor about all medicines currently or recently taken, as well as any medicines the patient plans to use.
In particular, inform your doctor if the patient is taking:
probenecid (used in the treatment of gout) – when administered concomitantly with Cloxacillin Polpharma, may increase
the antibiotic's serum concentration;
anticoagulant medicines (medicines preventing blood clots), such as warfarin – when used together with Cloxacillin Polpharma,
may increase the tendency to bleeding and lead to haemorrhage;
methotrexate (used in the treatment of arthritis): Cloxacillin Polpharma used together with methotrexate may increase its toxicity;
oral contraceptives: Cloxacillin Polpharma used together with oral hormonal contraceptives may reduce contraceptive efficacy.
The doctor will recommend using additional non-hormonal contraceptive methods;
ampicillin, fusidic acid (antibiotics), and Cloxacillin Polpharma – when used simultaneously, may enhance each other's effects;
erythromycin, tetracyclines, chloramphenicol (antibiotics): concomitant administration of Cloxacillin Polpharma with any of these
medicines may weaken its effect;
aminoglycoside antibiotics (e.g. streptomycin, gentamicin, neomycin) and Cloxacillin Polpharma are physically and chemically incompatible – these medicines should not be administered simultaneously;
proguanil (a medicine used in malaria treatment) may cause reduced 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 Cloxacillin Polpharma, urine glucose tests performed by certain methods may yield false-positive results; therefore, if such testing is necessary, enzymatic tests are recommended. Cloxacillin Polpharma may also alter urinary steroid assay results.

Pregnancy, breastfeeding and fertility
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, Cloxacillin Polpharma should be used during pregnancy only when, in the doctor's opinion, the potential benefits outweigh the possible risks.

Breastfeeding
The medicine passes into human milk in small amounts. Therefore, breastfeeding may need to be discontinued if the infant develops gastrointestinal disturbances (diarrhoea, candidiasis, or skin rash).

Effect on fertility
There are only limited data on the use of cloxacillin in humans. Animal studies on reproductive toxicity are insufficient.

Driving and operating machinery
There are no data on the effect of Cloxacillin Polpharma on the ability to drive or operate machinery. Therefore, if the patient experiences symptoms affecting concentration (e.g. headache, drowsiness; see section 4 "Possible adverse effects") or does not feel well, driving and operating machinery should be avoided.

Cloxacillin Polpharma contains sodium

Cloxacillin Polpharma 500 mg
Each 500 mg of the medicine contains 24.8 mg of sodium (main component of table salt). This corresponds to 1.24% of the maximum recommended daily sodium intake in the adult diet. This should be taken into account in patients controlling dietary sodium intake.

Cloxacillin Polpharma 1 g
Each 1 g of the medicine contains 49.6 mg of sodium (main component of table salt). This corresponds to 2.48% of the maximum recommended daily sodium intake in the adult diet. This should be taken into account in patients controlling dietary sodium intake.

Cloxacillin Polpharma 2 g
Each 2 g of the medicine contains 99.2 mg of sodium (main component of table salt). This corresponds to 4.96% of the maximum recommended daily sodium intake in the adult diet. This should be taken into account in patients controlling dietary sodium intake.

The medicine contains 600 mg of sodium (main component of table salt) in the maximum daily dose of 12 g of cloxacillin. This corresponds to 30% of the maximum recommended daily sodium intake in the adult diet. This should be taken into account in patients controlling dietary sodium intake.
When using solvents containing sodium (see "Information intended exclusively for healthcare professionals"), the amount of sodium derived from the solvent must be considered when calculating the total sodium content in the prepared diluted medicine. For this purpose, refer to the leaflet of the solvent used.

3. How to use Cloxacillin Polpharma

This medicine should always be used exactly as prescribed by the physician. In case of doubts, consult
your doctor or pharmacist.
Note: In severe infections, performing an antibiogram is recommended before initiating cloxacillin therapy.
Dosing
The physician determines the dose for each individual patient – the dose depends on the severity of the infection,
the susceptibility of the causative microorganism, and the patient's condition, age, and body weight.
Adults
Depending on the type and severity of infection, 1–2 g is administered intramuscularly or intravenously every 4–6
hours.
The maximum daily dose is 12 g.
Recommended dosing for specific infections in adults
Pneumonia caused by methicillin-sensitive Staphylococcus aureus
1–2 g intravenously or intramuscularly every 6 hours for 10–14 days.
Pyomyositis 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 over 4–6 weeks,
prosthetic valve – 12 g per day intravenously in 4–6 divided doses over 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,
intravenously or orally, for 6 weeks or longer.
Central nervous system infections caused by methicillin-sensitive Staphylococcus aureus
2 g intravenously every 4 hours.
Vascular catheter-related infections caused by methicillin-sensitive Staphylococcus aureus
2 g intravenously every 4–6 hours.
Toxic shock syndrome caused by methicillin-sensitive Staphylococcus aureus
1–2 g intravenously every 4 hours.
Patients with cystic fibrosis
Compared to the control/healthy group – a significant increase in the volume of distribution of cloxacillin has been observed, as well as three times faster elimination (2.5-fold increase in extrarenal clearance).
In this patient group, higher doses should be considered and serum cloxacillin concentrations should be monitored.
Dosing in patients with renal impairment
Patients with renal impairment should inform their physician before receiving Cloxacillin Polpharma.
The physician will determine an individualized dosing regimen depending on the degree of renal impairment (see section 2 "Warnings and precautions").
Children and adolescents
Administer intravenously.
Treatment of hospital-acquired infections in newborns, infants, and children:

• newborns aged 0–7 days, body weight <2 kg: 25 mg/kg body weight every 12 hours (50 mg/kg body weight per day),
• newborns aged 0–7 days, body weight ≥2 kg: 25 mg/kg body weight every 8 hours (75 mg/kg body weight per day),
• newborns aged 8–28 days, body weight <2 kg: 25 mg/kg body weight every 8 hours (75 mg/kg body weight per day),
• newborns aged 8–28 days, body weight ≥2 kg: 37.5 mg/kg body weight every 6 hours (150 mg/kg body weight per day),
• infants, children, and adolescents: 37.5 mg/kg body weight every 6 hours (150 mg/kg body weight per day).

Treatment of severe infections such as bacterial meningitis:

• newborns aged 0–7 days, body weight <2 kg: 37.5 mg/kg body weight every 12 hours (75 mg/kg body weight per day),
• newborns aged 0–7 days, body weight ≥2 kg: 25 mg/kg body weight every 8 hours (75 mg/kg body weight per day),
• newborns aged 8–28 days, body weight <2 kg: 50 mg/kg body weight every 8 hours (150 mg/kg body weight per day),
• newborns aged 8–28 days, body weight ≥2 kg: 50 mg/kg body weight every 6 hours (200 mg/kg body weight per day),
• infants, children, and adolescents: 50 mg/kg body weight every 6 hours (200 mg/kg body weight per day).

In children and adolescents, the maximum daily dose of cloxacillin is 12 g.
Treatment of severe infections such as infective endocarditis caused by Staphylococcus spp: the cloxacillin dose may be increased up to 300 mg/kg body weight per day in 4–6 divided doses.
If during treatment the patient feels that the effect of the medicine is too strong or too weak, consult the physician.
Duration of treatment
The duration of treatment depends on the severity and type of infection and the patient's clinical condition.
The physician will determine the appropriate duration of treatment, which must be strictly followed.
Method of administration
The method of administration and preparation of solutions is provided at the end of this leaflet, in the section “Information intended exclusively for healthcare professionals”.
Use of a higher than recommended dose of Cloxacillin Polpharma
Since Cloxacillin Polpharma will be administered by a physician or nurse, incorrect dosing is unlikely. However, if the patient suspects that an excessive dose has been administered, they should immediately inform the physician.
Missed dose of Cloxacillin Polpharma
Do not administer a double dose to make up for a missed dose.
Discontinuation of Cloxacillin Polpharma
It is important that the medicine is used according to the prescribed treatment regimen. Do not discontinue treatment just because the patient feels better. Premature discontinuation of treatment may result in recurrence of the infection. If the patient feels worse during treatment or does not feel well after completing the prescribed treatment course, they should contact the physician. In case of any further doubts regarding the use of this medicine, consult the physician, pharmacist, or nurse.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone experiences 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 frequently than in 1 out of 10,000
people):
allergic reactions, immediate allergic reactions such as sudden shortness of breath and chest tightness, eyelid, facial or lip swelling, severe skin rashes which may involve blistering affecting the eyes, mouth, throat and genital organs, loss of consciousness (fainting). Delayed allergic reactions (may appear 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 progressing severe rash with blisters or skin peeling 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), serum sickness-like symptoms such as skin urticaria with burning sensation, allergic vasculitis.
Diarrhea that is severe, persistent over a long period, or containing blood, occurring with 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 (no more than in 1 out of 10 people):

• diarrhea.

The following adverse reactions occur rarely (no more than in 1 out of 1,000 people):

• skin redness at the injection site or thrombophlebitis.

The following adverse reactions occur very rarely (less than in 1 out of 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 hairy tongue;
• anuria, interstitial nephritis, tubular dysfunction. Symptoms of these disorders most commonly include rash, fever, increased number of one type of granulocytes in the blood, hematuria, proteinuria. These usually occur in patients receiving high doses of the drug and (or) with pre-existing renal function disorders and resolve upon discontinuation of the drug;
• transient hyperkinesia, agitation, restlessness, drowsiness, disorientation and (or) dizziness. These symptoms usually occur in patients with renal impairment receiving high doses of the drug;
• elevated liver enzyme activity; in isolated cases, hepatitis may occur, along with jaundice (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 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
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.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Cloxacillin Polpharma

Unopened vial: No special storage conditions required.
Storage conditions after vial opening and preparation of the solution are provided in the section
"Information intended exclusively for healthcare professionals".
Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after EXP.
The expiry date refers to the last day of the stated month.
The marking on the packaging following the abbreviation EXP indicates the expiry date, and following the abbreviation Lot indicates the batch number.
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 Cloxacillin Polpharma contains

• The active substance is cloxacillin in the form of cloxacillin sodium. Each vial contains 500 mg, 1 g or 2 g of cloxacillin as cloxacillin sodium. The medicinal product contains sodium – see section 2 of the patient leaflet.
• The medicinal product does not contain any other ingredients.

What Cloxacillin Polpharma looks like and contents of the pack
Cloxacillin Polpharma is a white or almost white, crystalline powder.
pH value of the prepared solution: 5–7.

Cloxacillin Polpharma 500 mg:
Vial with a capacity of 8 ml made of colourless glass (type III), with a chlorobutyl rubber stopper (type I),
aluminium cap and plastic flip-off seal.
Vial with a capacity of 8 ml made of colourless glass (type III), with a chlorobutyl rubber stopper (type I),
aluminium cap.
Pack: 10 vials containing 500 mg of cloxacillin each, in a cardboard box.

Cloxacillin Polpharma 1 g:
Vial with a capacity of 20 ml made of colourless glass (type III), with a chlorobutyl rubber stopper (type I),
aluminium cap and plastic flip-off seal.
Vial with a capacity of 20 ml made of colourless glass (type III), with a chlorobutyl rubber stopper (type I),
aluminium cap.
Pack: 10 vials containing 1 g of cloxacillin each, in a cardboard box.

Cloxacillin Polpharma 2 g:
Vial with a capacity of 20 ml made of colourless glass (type III), with a chlorobutyl rubber stopper (type I),
aluminium cap and plastic flip-off seal.
Vial with a capacity of 20 ml made of colourless glass (type III), with a chlorobutyl rubber stopper (type I),
aluminium cap.
Pack: 10 vials containing 2 g of cloxacillin each, in a cardboard box.

Marketing Authorisation Holder
POLPHARMA S.A. Pharmaceutical Works
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. + 48 22 364 61 01

Manufacturer/Importer
Medochemie Ltd (Factory B – Injectable Facility)
Agios Athanassios Industrial Area, Iapetou 48,
Limassol, 4101, Cyprus

Information intended exclusively for medical professionals:

Before administration, the solution should be inspected visually. The solution should only be administered if it is
clear and practically free from visible particles.

Administration method
The medicinal product can be administered via intramuscular or intravenous injection, by intravenous infusion, or
by injection into the pleural cavity (no established dosage of cloxacillin for administration into the pleural cavity).

Intramuscular injection
The medicinal product should be injected into large muscle groups.
Doses exceeding 1 g should be administered at two different sites.

Intravenous injection (bolus)
For intravenous injections (bolus), cloxacillin should be administered over 2 to 10 minutes.

Intravenous infusion
For intravenous infusion, cloxacillin should be administered over 30 to 40 minutes.

Preparation of solutions

Intramuscular injection

• 500 mg of powder should be dissolved in 2 ml of water for injections or 0.9% sodium chloride solution.
• 1 g of powder should be dissolved in 4 ml of water for injections or 0.9% sodium chloride solution.
• 2 g of powder should be dissolved in 8 ml of water for injections or 0.9% sodium chloride solution.

Intravenous injection

• 500 mg of powder should be dissolved in 10 to 20 ml of water for injections or 0.9% sodium chloride solution. Administer slowly over 2 to 10 minutes.
• 1 g of powder should be dissolved in 20 to 40 ml of water for injections or 0.9% sodium chloride solution. Administer slowly over 2 to 10 minutes.
• 2 g of powder should be dissolved in 20 to 40 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 up to 12 hours at a temperature below 25°C.

Intravenous infusion

• Cloxacillin Polpharma 500 mg: Dissolve the contents of the 500 mg vial in 2 ml of water for injections, then dilute with:
  • 0.9% sodium chloride solution
  • or 5% glucose solution to a final volume of 50 ml to 500 ml. Administer over 30 to 40 minutes. Concentration exceeding 40 mg/ml is not recommended.
• Cloxacillin Polpharma 1 g: Dissolve the contents of the 1 g vial in 4 ml of water for injections, then dilute with:
  • 0.9% sodium chloride solution
  • or 5% glucose solution to a final volume of 50 ml to 500 ml. Administer over 30 to 40 minutes. Concentration exceeding 40 mg/ml is not recommended.
• Cloxacillin Polpharma 2 g: Dissolve the contents of the 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 to 500 ml. Administer over 30 to 40 minutes. Concentration exceeding 40 mg/ml is not recommended.

The prepared solution may be stored in polyolefin containers (including polyethylene - PE containers) for 12 hours at a temperature below 25°C or for 48 hours at a temperature of 2°C to 8°C (in a refrigerator).